The increasing prevalence of overweight and obesity globally has heightened the risk of non-communicable diseases, including type 2 diabetes (T2D) and cardiovascular disease (CVD). A significant contributor to these complications is the Westernized diet, characterized by high levels of saturated fat and added sugar, coupled with low dietary fiber. In particular, added sugar increases the energy density of diets, potentially leading to increased energy intake and the development of obesity. Consequently, strategies to reduce sugar intake, such as replacing it with sugar substitutes and sweeteners (S&SEs), have gained traction.
The Role of Sugar Substitutes and Sweeteners (S&SEs)
Worldwide consumption of foods and beverages containing S&SEs has increased substantially. While generally considered safe, the long-term effects of S&SEs on cardiometabolic health remain a topic of debate. Some cohort studies have raised concerns about potential risks, leading the World Health Organization (WHO) to issue a conditional recommendation against using non-sugar sweeteners for weight control or reducing the risk of non-communicable diseases. However, observational evidence does not always align with data from short-term studies, and some long-term randomized controlled trials (RCTs) have shown neutral or beneficial effects, including modest weight loss and no negative impact on T2D or CVD risk markers.
Potential Impact on Gut Microbiota
An emerging concern is the potential impact of S&SEs on gut microbiota composition, with some studies suggesting that S&SEs may alter the gut microbiota, potentially affecting metabolic health. One study demonstrated a link between saccharin-induced alterations in the gut microbiota and glucose intolerance in mice. A small post hoc human trial showed that supplementation of saccharin increased glycaemic response, which was associated with microbiota alterations in a small group of study participants. The microbiota composition of responders was distinct before saccharin exposure, suggesting individual variability in response to S&SEs and the potential for the gut microbiome to predict susceptibility.
However, other studies and a crossover RCT found no effect of saccharin, sucralose, or aspartame on gut microbiota or glucose regulation after 2 weeks in healthy individuals. These conflicting results highlight the controversy in the current evidence, emphasizing the need for controlled, long-term studies to directly assess the impact of replacing sugar with S&SEs on microbiota and metabolic outcomes.
The SWEET Project RCT
The SWEET project was designed to assess the effect of combined and prolonged use of S&SEs (in both foods and drinks)-as part of a healthy sugar-reduced ad libitum diet-on weight loss maintenance, cardiometabolic risk factors, and gut microbiota composition in adults with overweight or obesity. The trial also focused on weight control and cardiometabolic outcomes in children with overweight or obesity.
Read also: Weight Loss Guide Andalusia, AL
The hypothesis was that the inclusion of S&SEs in foods and drinks would increase the palatability of the diet and thereby compliance with the recommendations for a healthy sugar-reduced diet, resulting in improved control of body weight and related risk factors, with no effect on gut microbiota or other safety concerns associated with their long-term use compared with a diet excluding S&SEs. The primary outcomes were 1-year changes in body weight and gut microbiota composition in adults. Secondary outcomes included 1-year changes in risk factors for T2D and CVD, body mass index (BMI)-for-age z-score in children, intrahepatic lipid (IHL) content, the occurrence of (serious) adverse events (AEs), gastrointestinal symptoms and use of concomitant medication in adults with overweight or obesity.
Results of the SWEET Project
In total, 341 adults and 38 children were included, with 203 adults and 22 children completing the 1-year trial. The 277 adults who completed the weight loss period lost 10.1 ± 3.6 kg with no difference between the groups. For children, the changes in body weight, height and BMI-for-age z-score did not differ between the groups. Waist and hip circumferences were also reduced with no differences between groups.
The 1-year change in adult body weight was −6.4 ± 6.5 kg for the whole intention-to-treat (ITT) population. For the ITT population, the S&SEs group maintained a 1.6 ± 0.7 kg larger weight loss than the sugar group. An interaction between time and intervention group was observed, with the sugar group weighing more than the S&SEs group at M4, M6, M9 and M12.
The clinical characteristics of the subgroup analysed for gut microbiota (n = 137) were comparable to those of the total adult population (n = 341). The gut microbiota subgroup showed significantly lower body weight regain in the S&SEs group compared to the sugar group over 1 year.
We observed a significant interaction between overall microbiota composition change in time and intervention group. A total of 46 taxa exhibited differential trends in relative abundance over time between the groups. The distinct shift in microbial communities between groups over time revealed increased overall abundance of multiple short-chain fatty acid (SCFA)-producing genera in the S&SEs group. Only three genera-Saccharimonadales, Candidatus Competibacter and Clostridium sensu stricto 1-exhibited lower abundance in the S&SEs group compared to the sugar group.
Read also: Beef jerky: A high-protein option for shedding pounds?
Xylitol and Erythritol: Impact on Glucose Absorption
Xylitol and erythritol are naturally occurring sugar alcohols of interest as alternative sweeteners. Studies in rodent models have shown that their acute ingestion reduces intestinal glucose absorption.
One study investigated whether a chronic intake of xylitol and erythritol impacts glucose absorption in humans with obesity. Forty-six participants were randomized to take either 8 g of xylitol or 12 g of erythritol three times a day for five to seven weeks, or to be part of the control group (no substance). Before and after the intervention, intestinal glucose absorption was assessed during an oral glucose tolerance test with 3-Ortho-methyl-glucose (3-OMG). The effect of xylitol or erythritol intake on the area under the curve for 3-OMG concentration was not significant.
Study Design and Methods
This study was a secondary endpoint analysis of two different clinical trials having the same intervention (except for intervention durations of 5 and 7 weeks for trial 1 and trial 2, respectively) in the same participant population. A total of 46 participants with obesity but without diabetes took part in this study. Participants were randomly assigned to one of the two intervention groups (consumption of either xylitol or erythritol every day for five weeks for trial 1 and seven weeks for trial 2) or the control group (no substance). In the intervention groups (but not in the control group), the trials were double-blinded.
During the intervention period of five or seven weeks, participants in the intervention groups were asked to consume pre-portioned sticks of either 8 g of pure xylitol or 12 g of pure erythritol dissolved in water three times per day, before the main meals. Participants in the control group did not consume any substance. Before and after the intervention period, all participants received a standardized glucose solution containing 75 g of glucose and 3 g of 3-OMG. At regular time intervals after administration of the solution, blood samples were taken for the analysis of plasma 3-OMG.
Results and Discussion
All subjects tolerated the study well, and there were no adverse events that led to study discontinuation. The effect of xylitol or erythritol intake on 3-OMG iAUC120 was not significant. Neither the time (pre or post intervention), nor the group (control, xylitol, or erythritol), nor the time-by-group interaction effects were significant.
Read also: Inspiring Health Transformation
These results are in contrast to findings that acute feeding of erythritol and xylitol in rats reduced intestinal glucose absorption, and to results that reported reduced glucose absorption after small intestinal perfusion of xylitol and glucose in rats. However, those studies were performed in animal models, and a direct extrapolation to the results in humans is not possible.
The regulation of glucose absorption depends in part on the availability of the two types of glucose transporters: SGLT-1 and GLUT2. While SGLT-1 is responsible for glucose absorption up to concentrations of about 30-50 mM of glucose in the lumen, GLUT2 is required to absorb glucose at higher concentrations.
Xylitol's Effects on Lipid Metabolism and Visceral Fat Accumulation
During the last decade, obesity has become a growing global health problem. The overconsumption of sugar in the standard diet has had devastating effects on people. One of the ways to iron out these problems is by finding a better sweetener as an alternative to sugar. From a health perspective, xylitol, the five-carbon sugar alcohol had previously reported to have many beneficial health effects. 40 grams per day of xylitol intake orally is safe and well tolerated on both humans and rodents. After administration, lesser insulin is released by xylitol compared to glucose. This is a good thing for those who are concerned with their body weight, as well as for the insulin-sensitive individuals.
Suppression of visceral fat accumulation had been found in rats given high fat diet supplemented with xylitol. At the same time, it also suppressed the insulinemia and lipidemia by significantly lowers the plasma insulin and triglyceride concentration. The long term intake of xylitol has been found to induce the expression of beta oxidation genes which promote the lypolysis in the liver and adinopect in genes in the adipose tissues. The finding exhibited that xylitol is safe to take in a long period of time.
Animal Studies
All mice were fed with high fat diets and normal drinking water to become the induced-obesity model. After being obese, all mice were divided into three different groups which were control, glucose and xylitol. Each group was administered with three different water solutions as their source of fluid. The normal drinking water was for control group, 10% glucose water was for glucose group and 10% xylitol water was for xylitol group. At this moment, all mice were fed with standard diets.
Xylitol mice shows the highest body weight loss and daily food intake. The cholesterol level in xylitol mice has the same mean value with the control mice group. The highest total cholesterol was found in the glucose mice.
Our data shows xylitol mice experienced the highest weight reduction compared to other groups. One of it is the gastric emptying time. The slower gastric emptying time for the digestion and absorption of nutrients affects the body weight loss. Previous studies have reported that the consumption of xylitol had significantly prolonged the gastric emptying time. It not only prolongs gastric emptying time but also concomitantly accelerates the intestinal transit of nutrients compared to glucose when fed as a single oral dose. The parenteral infusion of glucose substitutes including xylitol has been reported to have several health benefits, such as anti-ketogenic effect, small damaging effect towards vein as well as increased in metabolism . Compared to glucose, xylitol consumption is more rapidly followed by high glycogen storage in the liver . Later this will reduce the generation of glucose from amino acids through gluconeogenesis .
This study also demonstrates a significant effect by xylitol towards the level of total cholesterol, triglycerides and LDL. This might be because xylitol supplementation has the ability in suppressing hepatic triglycerides and other cholesterol concentrations of mice induced by high-fat diet. Islam (2011) has reported that xylitol has significant effects in most serum lipids of animal lab. In addition, a recent study by Amo et al. (2011) reported that 8 weeks feeding of xylitol could significantly decrease the serum lipid profile in normal rats fed with a high-fat diet except for HDL-cholesterol, although the food intake data was not presented in their report. Their data showed intake of xylitol induced the expression of lipid degradation and adiponectin genes in the adipose tissues, as well as fatty acids beta oxidation genes, which catabolised the long chain fatty acids in the liver. Tamura et al. (2013) reported that plasma total cholesterol concentration in their xylitol-fed mice is also significantly lower than the control group . They suggested that dietary xylitol has a modest effect towards lipid absorption in mice. It also reported that total serum cholesterol level was significantly lower in xylitol rats compared to the control group .
From the present finding, the supplementation of xylitol was found to have potential effects against lowering lipid profile measurement of DIO mice, as evidence by biological assessment and chemical analysis finding. The most significant effects were observed in xylitol group which showed improvement and reduction of lipid profile measurement.
Further Research on Xylitol and Lipid Metabolism
Here we investigated the effects of dietary xylitol on lipid metabolism and visceral fat accumulation in rats fed a high-fat diet. Sprague-Dawley rats were fed a high-fat diet containing 0 g (control), 1.0 g/100 kcal (X1) or 2.0 g/100 kcal (X2) of xylitol. After the 8-week feeding period, visceral fat mass and plasma insulin and lipid concentrations were significantly lower in xylitol-fed rats than those in high-fat diet rats. Gene expression levels of ChREBP and lipogenic enzymes were higher, whereas the expression of sterol regulatory-element binding protein 1c was lower and fatty acid oxidation-related genes were significantly higher in the liver of xylitol-fed rats as compared with high-fat diet rats.
During the 8-week feeding period, the energy intake was similar in all groups. After the experimental period, body weight did not differ among the groups; however, the accumulation of visceral fat was significantly smaller in the xylitol-fed (X1 and X2) groups than in the control (HFD) group. In particular, the relative weight of mesenteric fat was significantly lower in the xylitol-fed (X2) group than in the HFD group by 23.2%. In addition, the relative weight of epididymal fat was significantly lower in the xylitol-fed (X1 and X2) groups than in the HFD group by 15.5% and 17.0%, respectively.
The plasma glucose and non-esterified fatty acid (NEFA) concentrations did not differ among the three groups. The plasma insulin and triglyceride concentrations were significantly lower in the xylitol-fed (X2) group than in the HFD group by 29.3% and 54.5%, respectively.
The adipose tissue of xylitol-fed rats showed significantly higher levels of mRNAs encoding PPARγ, adiponectin, HSL and ATGL. These data indicates a miniaturization of adipocytes and lipolysis were caused in the adipose tissue, that they could contribute to lowering fat mass in xylitol-fed rats.
In the liver, the mRNA levels of ChREBP, and the lipogenic enzymes ACC and FAS were higher in the xylitol-fed (X1 and X2) groups than in the HFD group. On the other hand, the mRNA level of another lipogenic transcription factor SREBP-1c, which regulated principally by insulin, was significantly lower in the xylitol-fed (X2) group than in the HFD group. The mRNA levels of the transcription factors PPARα and PPARγ coactivator 1α (PGC-1α) which regulate fatty acid oxidation were significantly higher in the xylitol-fed (X2) group than in the HFD group. The mRNA levels of acyl-coenzyme A oxidase (ACO) and uncoupling protein 2 (UCP2), downstream target genes of PPARα were significantly higher in the xylitol-fed (X1 and X2) groups than in the HFD group.
In the long-term xylitol feeding test, fasting plasma insulin level was reduced in the xylitol-fed groups than in the HFD group. In oral sucrose tolerance test, xylitol supplementation exhibited a suppression of postprandial hyperglycemia. Therefore, the suppression of plasma insulin levels in xylitol-fed rats of the long-term test could be attributed to the suppression of postprandial hyperglycemia.
Recent Findings on Xylitol and Cardiovascular Risk
Recent research has raised concerns about the potential cardiovascular risks associated with xylitol. An observational study published in the June issue of European Heart Journal found that high levels of xylitol were associated with greater risk of heart attack or stroke in adults years later.
Additional lab and animal research presented in both papers revealed erythritol and xylitol may cause blood platelets to clot more readily. In the new study on xylitol, “differences in platelet behavior were seen even after a person consumed a modest quantity of xylitol in a drink typical of a portion consumed in real life,” said Dr.
They found a number of alcohol sugars that appeared to have an impact on cardiovascular function, including xylitol and erythritol. “There’s a receptor on our platelets, which we as yet don’t understand, that is recognizing this molecule and signaling to the platelet to be more prone to clot,” he said.
Reducing clotting activity is a key treatment used by cardiologists, so any additional clotting in platelets is a bad sign, said Dr. Some 12-ounce drinks that use xylitol as a major artificial sweetener can contain 30 grams or more,” he said. “Yet people at risk for diabetes are among the most vulnerable for clotting events,” he said.