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Effect of steviol glycosides on systolic blood pressure (mm Hg). CI: confidence interval; MD: mean difference; RCTs: randomised clinical trials; SD: standard deviation.
Source publication
Introduction:
Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular...
Citations
... Many studies indicate that it may be especially beneficial for the prevention of dental caries, diabetes, heart disease, hypertension, obesity, and heart problems (Onakpoya & Heneghan, 2015). ...
... Nevertheless, given their safeness, high sweetness with low-calorie value, and favorable impact on glucose metabolism, SGs may have the potential to serve as sugar substitutes for effective control of obesity. 42 In addition, because inadequately elevated blood glucose levels are well known as being a significant risk factor for T2DM and CVD, [43][44][45] lowering and managing glucose levels become the most effective strategy for prevention of T2DM and CVD. [46][47][48] Therefore, the effect of SGs on reduced FBG may generate new insights into the control and prevention of obesity, T2DM and its complications, CVD and deaths, from the perspective of functional food and dietary sweeteners. ...
... There have been three meta-analyses summarizing the evidence for the effects of SGs on glucose metabolism. 21,42,58 Chowdhury et al. 58 performed a pooled analysis of animal studies, showing a significant benefit to blood glucose control. Another meta-analysis based on six RCTs reported a mild and significant reduction in FBG (MD = −0.63 ...
... mg dl −1 , CI −0.90 to −0.36) in SGs. 42 In contrast, an updated meta-analysis, published in 2019, included seven RCTs (six full-text reports and one abstract) and showed no significant difference in FBG (MD = −2.63 mg dl −1 , CI −7.77 to 2.51) between SGs and the control. ...
SGs as safe natural sweeteners, may yield significant improvement in glucose metabolism in adult participants when compared with the control.
... The physiological actions of RebA are still unclear due to the high heterogeneity of studies, the huge differences in doses used, the times of intervention, and stevia derivatives. In a systematic review with meta-analysis including 756 participants, RebA did not improve blood pressure or cardiovascular risk in contrast to stevioside, which seems to decrease blood pressure and fasting glycemia, although the small effect and the robustness of the results are limited to the heterogeneity of the studies included [42]. ...
The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.
... In the past decade, stevia extracts and steviol glycosides have been recognized as safe by the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) 16,17 . In line with this, a systematic review and meta-analysis of randomized clinical trials established that the use of purified RebA does not have any significant effect on blood pressure, fasting blood glucose or lipid profile, hence supporting the idea that steviol glycosides represent a safer alternative among the NAS 18 . ...
Overconsumption of added sugars has been pointed out as a major culprit in the increasing rates of obesity worldwide, contributing to the rising popularity of non-caloric sweeteners. In order to satisfy the growing demand, industrial efforts have been made to purify the sweet-tasting molecules found in the natural sweetener stevia, which are characterized by a sweet taste free of unpleasant aftertaste. Although the use of artificial sweeteners has raised many concerns regarding metabolic health, the impact of purified stevia components on the latter remains poorly studied. The objective of this project was to evaluate the impact of two purified sweet-tasting components of stevia, rebaudioside A and D (RebA and RebD), on the development of obesity, insulin resistance, hepatic health, bile acid profile, and gut microbiota in a mouse model of diet-induced obesity. Male C57BL/6 J mice were fed an obesogenic high-fat/high-sucrose (HFHS) diet and orally treated with 50 mg/kg of RebA, RebD or vehicle (water) for 12 weeks. An additional group of chow-fed mice treated with the vehicle was included as a healthy reference. At weeks 10 and 12, insulin and oral glucose tolerance tests were performed. Liver lipids content was analyzed. Whole-genome shotgun sequencing was performed to profile the gut microbiota. Bile acids were measured in the feces, plasma, and liver. Liver lipid content and gene expression were analyzed. As compared to the HFHS-vehicle treatment group, mice administered RebD showed a reduced weight gain, as evidenced by decreased visceral adipose tissue weight. Liver triglycerides and cholesterol from RebD-treated mice were lower and lipid peroxidation was decreased. Interestingly, administration of RebD was associated with a significant enrichment of Faecalibaculum rodentium in the gut microbiota and an increased secondary bile acid metabolism. Moreover, RebD decreased the level of lipopolysaccharide-binding protein (LBP). Neither RebA nor RebD treatments were found to impact glucose homeostasis. The daily consumption of two stevia components has no detrimental effects on metabolic health. In contrast, RebD treatment was found to reduce adiposity, alleviate hepatic steatosis and lipid peroxidation, and decrease LBP, a marker of metabolic endotoxemia in a mouse model of diet-induced obesity.
... It is believed to be a result of the research' data being inconsistent and incomparable. Further clinical research and regulatory assessments are required [27]. ...
Stevia rebaudiana Bertoni or stevia represents a branched small perennial shrub from the Asteraceae family. Stevia derivates are available on the market in the form of tablets, powder and liquid. It is used in herbal medicines (diabetic tonics), food industry (confectionery, desserts, ice cream, sauces, ketchup, drinks, soft drinks, formulas for athletes) as well as cosmetics (toothpastes and mouthwashes). The feeling of sweetness in stevia is caused by steviol glycosides. The four primary steviol glycosides: stevioside, rebaudioside A, rebaudioside C, dulcoside A. Stevia is a natural non-nutritive intensive sweetener that has a significant advantage over other sweeteners (sucrose and artificial sweeteners) as a food industry ingredient. It can be used as a sucrose replacement in beverages and food products. Stevia enhances the taste of food, helps digestion, weight loss, has antioxidant and antimicrobial action, prevents tooth decay among diabetics and healthy people who care about their health. In the future, stevia is probably going to play a significant role in the supply of high strength sweeteners for the expanding natural food market.
... Evaluation of secondary parameters revealed no clinically significant change in PPBG level, total cholesterol, LDL, VLDL, triglyceride, and HbA1c from baseline to Day 90, and all the values were within the normal laboratory range. This was similarly reported in several clinical studies [22][23][24][25][26][27]. A decrease in PPBG level was observed in overweight healthy subjects with normal sugar levels, which was significant at Day 30 and Day 60, although non-significant at Day 90. ...
Unlabelled:
Added sugars contribute to caloric intake in the diet, which may lead to conditions like obesity. Replacing added sugar with a natural sugar substitute like zero-calorie stevia may help in reducing sugar and caloric intake.
Methods:
An open-label, single-arm pilot study was conducted to evaluate the efficacy and safety of a stevia-based tabletop sweetener among overweight subjects with normal blood sugar levels (n = 24) and overweight prediabetic subjects (n = 21). Subjects were instructed to replace added sugar in their daily diet with the test product over a study period of 90 days. Primary outcomes included change in body weight and waist circumference, while the secondary outcomes included change in blood glucose (PPBG), body mass index (BMI), and lipid parameters evaluated at baseline, 30 days, 60 days, and 90 days. Glycated hemoglobin (HbA1c) was evaluated at baseline and 90 days.
Results:
When compared with the baseline, a significant reduction in weight (p < 0.001) and waist circumference (p < 0.001) was observed at Day 90 in overweight subjects. Similarly, in overweight prediabetic subjects, a significant reduction in weight (p < 0.001) and waist circumference (p < 0.05) with non-significant change in HbA1c was observed at Day 90 from baseline. In a subgroup analysis, among the subjects who lost weight, 2.12 kg (n = 35) weight loss and 4.78 cm (n = 32) reduction in waist circumference were observed at 90 days. No adverse outcomes were reported throughout the study period. The consumption of steviol glycosides was within the acceptable daily intake (ADI).
Conclusions:
Replacing added sugar in the daily diet with stevia-based tabletop sweetener, along with a physical activity regimen, promotes weight loss and reduction in waist circumference in overweight subjects with normal blood sugar levels and prediabetic subjects (CTRI/2019/12/022470).
... Considering that the metabolites of steviol glycosides are actually responsible for its glycemic effects [7,9,26,27], one may question how effects can be observed immediately after steviol glycoside intake and what the effect would be at maximal metabolite presence. Following chronic administration, the meta-analyses of Onakpoya et al. and Anker et al. suggested, respectively, a significant lower fasting blood glucose overall and non-significant reductions in fasting blood glucose and HbA1c in T2DM subgroups after intake of steviol glycosides, but they concluded that more studies are needed regarding the effect of steviol glycosides on T2DM biomarkers [25,31]. For a follow-up study, one could consider that higher exposure to steviol and steviol glucuronide could be reached by chronic administration of high doses of steviol glycosides, resulting in a glycemic benefit in those subjects with well-preserved β-cell function. ...
Background and Objectives
Rebaudioside A, a steviol glycoside, is deglycosylated by intestinal microflora prior to the absorption of steviol and conjugation to steviol glucuronide. While glucose-lowering properties are observed for rebaudioside A in mice, they have been attributed to the metabolites steviol and steviol glucuronide. We aimed to characterize the pharmacokinetic and pharmacodynamic properties of rebaudioside A and its metabolites in patients with early-onset type 2 diabetes mellitus (T2DM).Methods
This randomized, placebo-controlled, open-label, two-way crossover trial was performed in subjects with T2DM on metformin or no therapy at the University Hospitals Leuven, Belgium. Following oral rebaudioside A (3 g), plasma concentrations of rebaudioside A, steviol and steviol glucuronide were determined. The effect on glucose homeostasis was examined by an oral glucose tolerance test (OGTT) performed 19 h following rebaudioside A administration, i.e. the presumed time of maximal steviol and steviol glucuronide concentrations. The primary pharmacodynamic endpoint was the difference in area under the blood glucose concentration–time curve during the first 2 h of the OGTT (AUCGlucose(0–2h)) for rebaudioside A vs. placebo.ResultsIn total, 30 subjects [63.5 (57.8–69.0) years of age, 86.7% male] completed the trial. Rebaudioside A was detected as early as 1 h after administration in nearly all subjects. As expected, steviol and steviol glucuronide reached their maximal concentrations at 19.5 h following rebaudioside A administration. Rebaudioside A did not lower the AUCGlucose(0–2h) compared to placebo (− 0.7 (95% CI − 22.3; 20.9) h·mg/dL, P = 0.95). Insulin and C-peptide concentrations were also comparable between both conditions (P > 0.05).Conclusion
Rebaudioside A is readily absorbed after oral administration and metabolized to steviol and steviol glucuronide. However, no effect on glucose nor insulin or C-peptide excursion was observed during the OGTT at the time of maximal metabolite concentrations. Thus, no antidiabetic properties of rebaudioside A could be observed in patients with T2DM after single oral use.Clinical Trial RegistrationRegistered on ClinicalTrials.gov (NCT03510624).
... Some prior meta-analyses have exclusively studied the effect of specific alternative sweeteners; for instance, Onakpoya et al investigated the overall effects of steviol glycosides on cardiovascular risk factors. In accordance with our results, there was no significant effect on serum lipid profile (Onakpoya and Heneghan 2015); whilst in, Anker et al, the overall effects of steviol glycosides on human health with emphasis on type 2 diabetic biomarkers was investigated, and the authors reported similar findings to the present study (Anker, Rafiq, and Jeppesen 2019). Furthermore, Santos et al investigated the metabolic effects of aspartame on different outcomes in adulthood through a meta-analysis. ...
... In addition, according to Azeez et al, where the effects of saccharin consumption on lipid profile were evaluated in rats, saccharin consumption could lead to a decrease in lipid profile concentration (Azeez, Alkass, and Persike 2019). The perception of how NNS or stevia-based sweeteners affect lipid metabolism and lipid profile seems to be inconsistent and controversial in different animal studies; indeed, it is likely that the hypothesized mechanisms of actions reported in animal studies do not translate to tangible changes in humans (Onakpoya and Heneghan 2015). ...
It has been posited that Non-nutritive sweeteners (NNS) intake may affect lipid profile. However, its proven effects on lipid profile are unclear, as clinical studies on this topic have produced inconsistent results. To fill this gap in knowledge, this systematic review and meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of artificial- and stevia-based sweeteners consumption on lipid profile markers. To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, and EMBASE, using relevant keywords. A random-effect model was utilized to estimate the weighted mean difference (WMD) and 95% confidence (95% CI) for TG, TC, and LDL. On the other hand, a fixed-effect model was used to estimate the WMD and 95% CI for HDL. Fourteen RCTs were included in the present meta-analysis. The pooled analysis revealed that NNS did not affect TG (WMD:-1.31, 95% CI:-5.89, 3.27 mg/dl), TC (WMD:-2.27,95% CI:-7.61,3.07 mg/dl), LDL (WMD:1,95% CI: −2.72, 4.71 mg/dl), and HDL (WMD:0.06, 95% CI:-0.62,0.73 mg/dl). Subgroup analysis showed that NNS may be related to a small, but statistically significant, increase in LDL (WMD:4.23, 95% CI:0.50,7.96 mg/dl) in subjects with normal levels of LDL (<100 mg/dl). We found that consumption of artificial- and stevia-based sweeteners is not associated with lipid profile changes in adults. This study has been registered at PROSPERO (registration number: CRD42021250025).
... However, human data are much less clear-cut. Systematic reviews [17,18] of randomized controlled trials (RCTs), cohort, case-control, and cross-sectional studies, and case series/reports showed no clear effects of NNS on glucose control. ...
There is an association between the consumption of artificial sweeteners and Type 2 diabetes in cohort studies, but intervention studies do not show a clear elevation of blood glucose after the use of artificial sweeteners. The objective of this study was to examine whether two commonly used artificial sweeteners had an adverse effect on glucose control in normal-weight subjects, and in overweight and obese subjects when consumed for 2 weeks. In the study, 39 healthy subjects (body-mass index, kg/m2) (18–45) without Type 2 diabetes with an age of 18–75 years were randomly assigned to 0.6 L/day of an artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) or 0.6 L/day of mineral water for 2 weeks each in a crossover study. There was a 4 week washout period with no drinks consumed. Glucose levels were read by a continuous glucose monitor (CGM) during each 2 week period. A 75 g oral glucose-tolerance test (OGTT) was performed at the beginning and end of each intervention period. Blood samples were collected at baseline, and 1 and 2 h for glucose and insulin. A 2 week intake of artificially sweetened beverage (ASB) did not alter concentrations of fasting glucose and fasting insulin, the area under the curve (AUC) for OGTT glucose and insulin, the incremental area under the curve (iAUC) for OGTT glucose and insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and the Matsuda index compared with the baseline and with the changes after a 2 week intake of mineral water. Continuous 2 week glucose concentrations were not significantly different after a 2 week intake of ASB compared with a 2 week intake of mineral water. This study found no harmful effect of the artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) on glucose control when consumed for 2 weeks by people without Type 2 diabetes.
... Adapted from Preferred Reporting Items for Systematic Reviews and Meta-Analyses 50 AMSTAR-2, 56 4 of the 25 reviews were determined to be high quality, 58-61 5 were of moderate quality, [62][63][64][65][66] and 16 were of low or critically low quality. [67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] The low-and critically low-quality reviews were not considered further. ...
Introduction
Low-calorie sweeteners are increasingly prevalent in the food supply and their consumption has increased in recent decades. Although low-calorie sweeteners approved for use are considered safe from a toxicological perspective, their short- and long-term impacts on chronic disease risk remain uncertain. The aim of this review was to summarize the evidence from systematic reviews on low-calorie sweetener use and chronic conditions and risk factors in children and adults.
Methods
MEDLINE and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews of randomized and nonrandomized studies that considered low-calorie sweeteners in relation to type 2 diabetes, cardiovascular disease, cancer, anthropometric measures, hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and dental caries. Data were extracted from 9 reviews deemed of moderate or high quality on the basis of AMSTAR-2.
Results
Narrative synthesis suggested inconsistent evidence on low-calorie sweetener use in relation to chronic conditions and associated risk factors, with nonrandomized studies suggesting positive associations and randomized studies suggesting negative or no associations.
Conclusion
Continued research on the long-term health impacts of low-calorie sweeteners across all life stages is warranted.
