Effect Van Stevia
Known risk factors for pancreatic cancer include obesity, diet, and diabetes, implicating glucose consumption and regulation as a key player.Stevia, by contrast, has been the subject of relatively few studies, and the potential health benefits are based on extrapolation rather than direct testing.Here, we used longitudinal tracking of pancreatic acinar carcinoma development, growth, and lethality in a sensitized mouse model.Despite exposure to aspartame and stevia from the in utero stage onward, we found no disease modification activity, in either direction.These results contribute to the data on aspartame and stevia safety, while also reducing confidence in several of the purported health benefits.The association of obesity, diet, and T2D with pancreatic cancer illustrates the strong linkage to glucose intake and regulation, thereby identifying artificial sweeteners as an important topic for investigation.Epidemiological analysis of aspartame use identified additional risk of lymphoma (8), urinary track tumors (9), and prostate cancer (10).Overall, thorough review of the scientific literature has found no robust and convincing evidence for toxic effects, including cancer promotion (14–16).Nonetheless, aspartame remains controversial (17, 18), especially in the public sphere, with prominent media attention given to several anti-aspartame campaigners.Self-reported diet drink consumption is also not randomly assigned and will show correlation with other variables that may modify disease.For a rare disease such as pancreatic cancer, a risk modification of even 10-fold increase is thus unlikely to be picked up in most studies, driving the need for screening the dietary impact in sensitized animal models.In contrast to aspartame, stevia is widely cited in alternative medicine circles to have antitumor properties, albeit with little scientific foundation.Stevia and its derivatives were originally banned in some countries due to fear of potential carcinogenic properties; however, toxicology studies found physiological doses to be safe (20).The origin for the claim of antitumor properties can be traced back to studies of skin cancer formation in mice.While this may reflect antitumor properties, the experimental result could equally represent an anti-inflammatory or even a skin barrier enhancement function.With strong links to diabetes, glucose consumption and obesity, pancreatic cancer remains one of the strongest candidates to detect an oncogenic role, either promoting or suppressive, of artificial sweeteners.In the case of stevia, the near-complete absence of solid experimental data for dietary supplementation in cancer makes in vivo testing imperative.Through dietary supplementation and longitudinal magnetic resonance imaging (MRI), we find that neither aspartame nor stevia have any significant impact on pancreatic acinar carcinoma development, growth, or mortality.Mice were bred under specific pathogen-free conditions and from the time of breeder set-up were exclusively fed on a standard chow (ssniff® R/M-H) with either normal drinking water, or drinking water supplemented with either aspartame (0.035% w/v, Blackburn Distributions Ltd.) or stevia (0.02% w/v, Stevia Natura) ad libitum.Male mice were moved to conventional conditions at 7 weeks of age for longitudinal MRI, with continuation of the dietary restriction.All experimental procedures were carried out in accordance with the recommendations of the University of Leuven Animal Ethics Committee.The scanner was equipped with an actively shielded gradient set of 600 mT/m using a respiration triggered spin echo sequence with 50 continuous slices of 0.5 mm thickness in interlaced mode (acquisition parameters: repetition time = 6,000 ms, echo time = 15.9 ms, field of view = 4.0 cm × 6.0 cm, a matrix of 200×400, two dummy scans and two averages).Images generated by MRI were analyzed with ImageJ to identify tumors (National Institute of Health, Bethesda, USA).This dietary change was implemented at the point of breeder set-up, ensuring exposure at the in utero, neonatal, juvenile, and adult stage.These results indicate that even with lifelong exposure, high doses of supplementary aspartame or stevia do not alter pancreatic acinar carcinoma development, with either a positive or negative effect.From 7 weeks onward, mice were assessed through magnetic resonance imaging (MRI) for tumor detection and size.(A) Cumulative incidence of pancreatic cancer as a function of age at tumor onset, stratified by water supply (standard, aspartame, stevia) in male mice (n = 13, 12, 15).(B) Violin plots showing the mean, SD, and kernel probability density of the age at tumor onset under each dietary modification.Total predicted tumor volumes were normalized for variation in age of onset and for the exponential growth rate (Figures 3A–C).By this measure, no alteration in the tumor growth rate was observed in mice given either the aspartame or stevia supplement.Most TAg+ mice on standard drinking water survived for the entire observation period, limiting the ability to detect decreases in tumor-induced mortality; however, together these results argue against any profound effect of either aspartame or stevia on pancreatic acinar carcinoma growth or mortality induction.Additional of high level dietary aspartame or stevia does not modify the growth rates of pancreatic cancer.(D) Violin plots showing the mean, SD, and kernel probability density of the percentage of tumor volume increase every 2 weeks, averaged over the period of observation, under each condition in male mice.(D) Kaplan–Meier plot showing the overall pancreatic cancer survival in male mice on house, aspartame, and stevia diets (n = 13, 12, 15).The compound is rapidly metabolized into the constituent components (common amino acids) and is not found in the blood or urine of individuals that ingest it (27).Our study demonstrated no detectable impact of dietary aspartame with pancreatic acinar carcinoma risk, using a well-defined sensitized rodent model.Our results here also demonstrated no impact of dietary stevia on the kinetics of pancreatic acinar carcinoma.It is therefore likely that the pharmacological properties of studied S