Cleveland Clinic researchers found higher amounts of the sugar alcohol xylitol are associated with increased risk of cardiovascular events like heart attack and stroke. They confirmed the association in a large-scale patient analysis, preclinical research models and a clinical intervention study, published in the European Heart Journal.
Xylitol is a common sugar substitute used in sugar-free candy, gums, baked goods and oral products like toothpaste. Over the past decade, the use of sugar substitutes, including sugar alcohols and artificial sweeteners, has increased significantly in processed foods that are promoted as healthy alternatives.
The team, led by Stanley Hazen, MD, PhD, had also previously revealed a similar link between erythritol and cardiovascular risk last year. Xylitol is not as prevalent as erythritol in keto or sugar-free food products in the US but is common in other countries.
“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combatting conditions like obesity or diabetes,” said Dr Hazen. “It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot related events.”
In this new study, researchers identified that high levels of circulating xylitol were associated with an elevated three-year risk of cardiovascular events in an analysis of more than 3000 patients in the US and Europe. A third of patients with the highest amount of xylitol in their plasma were more likely to experience a cardiovascular event. To confirm the findings, the research team conducted pre-clinical testing and found that xylitol caused platelets to clot and heightened the risk of thrombosis. Researchers also tracked platelet activity from people who ingested a xylitol-sweetened drink versus a glucose-sweetened drink and found that every measure of clotting ability significantly increased immediately following ingestion of xylitol but not glucose.
The authors note that further studies assessing the long-term cardiovascular safety of xylitol are warranted. The research had several limitations, including that clinical observation studies demonstrate association and not causation.
Replacing sugar with artificial and natural sweeteners in foods has been the subject of a great deal of controversy, due to conflicting reports about their potential to increase appetite. But according to a significant new study published in eBioMedicine, it does not in fact make people hungrier as is often held – and also helps to reduce blood sugar levels.
Previous studies into whether sugar replacement with sweeteners increase appetite have been carried out but did not provide robust evidence. But the researchers say that their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake.
The double blind randomised controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods. Additionally, it was found to provide some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes.
The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe.
Lead author Catherine Gibbons, Associate Professor in the University of Leeds’ School of Psychology, said: “Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes.
“Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages.”
Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds’ School of Psychology, said: “The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases.
“Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control.”
Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycaemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes.
Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet.
The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity. Participants were all aged 18 to 60, with overweight or obesity.
The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14–21 days. Day 1 and day 14 of the consumption periods took place in the lab.
Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences.
After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide – hormones associated with the consumption of food.
The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels.
An analysis of UK Biokank data showed that adults who reported drinking two litres or more of sugar- or artificially sweetened drinks per week had a higher risk of atrial fibrillation compared with adults who drank fewer such beverages, according to new research published in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association.
The study also found that drinking one litre or less per week of pure, unsweetened juice, such as orange or vegetable juice, was associated with a lower risk of atrial fibrillation (AFib). However, the study could not confirm whether the sweetened drinks caused AFib, yet the association remained after accounting for a person’s genetic susceptibility to the condition.
Consuming sweetened drinks has been linked to Type 2 diabetes and obesity in previous research. This large study of health data in the UK Biobank is among the first to assess a possible link between sugar- or artificially sweetened beverages and AFib.
“Our study’s findings cannot definitively conclude that one beverage poses more health risk than another due to the complexity of our diets and because some people may drink more than one type of beverage,” said lead study author Ningjian Wang, MD, PhD, a researcher at the Shanghai Ninth People’s Hospital and Shanghai Jiao Tong University School of Medicine in Shanghai, China. “However, based on these findings, we recommend that people reduce or even avoid artificially sweetened and sugar-sweetened beverages whenever possible. Do not take it for granted that drinking low-sugar and low-calorie artificially sweetened beverages is healthy, it may pose potential health risks.”
The researchers reviewed data from dietary questionnaires and genetic data for more than 200 000 adults free of AFib at the time they enrolled in the UK Biobank, between 2006 and 2010. During the nearly 10-year follow-up period, there were 9362 cases of AFib among the study participants.
The analysis found:Compared to people who did not consume any sweetened drinks, there was a 20% increased risk of atrial fibrillation among people who said they drank more than 2 litres per week of artificially sweetened beverages; and a 10% increased risk among participants who reported drinking 2 litres per week or more of sugar-sweetened beverages.
People reporting 1 litre or less of pure fruit juice each week had an 8% lower risk of atrial fibrillation.
Participants who consumed more artificially sweetened beverages were more likely to be female, younger, have a higher body mass index and a higher prevalence of Type 2 diabetes.
Participants who consumed more sugar-sweetened beverages were more likely to be male, younger, have a higher body mass index, a higher prevalence of heart disease and lower socioeconomic status.
Those who drank sugar-sweetened beverages and pure juice were more likely to have a higher intake of total sugar than those who drank artificially sweetened drinks.
Smoking may have also affected risk, with smokers who drank more than two litres per week of sugar-sweetened beverages having a 31% higher risk of AFib, whereas no significant increase risk was noted for former smokers or people who never smoked.
“These novel findings on the relationships among atrial fibrillation risk and sugar- and artificially sweetened beverages and pure juice may prompt the development of new prevention strategies by considering decreasing sweetened drinks to help improve heart health,” Wang said.
Researchers also evaluated whether a genetic susceptibility to AFib was a factor in the association with sweetened beverages. The analysis found the AFib risk was high with the consumption of more than 2 litres of artificially sweetened drinks per week regardless of genetic susceptibility.
Eating more ultra-processed foods (UPFs) may be associated with a higher risk of developing cancers of the upper aerodigestive tract (ie, the mouth, throat and oesophagus), according to a new study in the European Journal of Nutrition. The authors of this study, led by the University of Bristol and the International Agency for Research on Cancer (IARC), say that obesity associated with the consumption of UPFs may not be the only factor to blame.
Several studies have identified an association between UPF consumption and cancer, including a recent study which looked at the association between UPFs and 34 different cancers in the largest cohort study in Europe, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which followed 450 111 adults who for approximately 14 years.
As more evidence emerges about the associations between eating UPFs and adverse health outcomes, researchers from the Bristol Medical School and IARC wanted to explore this further.
Since many UPFs have an unhealthy nutritional profile, the team sought to establish whether the association between UPF consumption and head and neck cancer and oesophageal adenocarcinoma in EPIC could be explained by an increase in body fat.
Results from the team’s analyses showed that eating 10% more UPFs is associated with a 23% higher risk of head and neck cancer and a 24% higher risk of oesophageal adenocarcinoma in EPIC.
Increased body fat only explained a small proportion of the statistical association between UPF consumption and the risk of these upper-aerodigestive tract cancers.
Fernanda Morales-Berstein, a Wellcome Trust PhD student at the University of Bristol and the study’s lead author, explained: “UPFs have been associated with excess weight and increased body fat in several observational studies. This makes sense, as they are generally tasty, convenient and cheap, favouring the consumption of large portions and an excessive number of calories. However, it was interesting that in our study the link between eating UPFs and upper-aerodigestive tract cancer didn’t seem to be greatly explained by body mass index and waist-to-hip ratio.”
The authors suggest that other mechanisms could explain the association.
For example, additives including emulsifiers and artificial sweeteners which have been previously associated with disease risk, and contaminants from food packaging and the manufacturing process, may partly explain the link between UPF consumption and upper-aerodigestive tract cancer in this study.
Fernanda Morales-Berstein and colleagues did caution that the associations between UPF consumption and upper-aerodigestive tract cancers found in the study could be affected by certain types of bias.
This would explain why they found evidence of an association between higher UPF consumption and increased risk of accidental deaths, which is highly unlikely to be causal.
Inge Huybrechts, Team head of the Lifestyle exposures and interventions team at IARC, added: “Cohorts with long-term dietary follow-up intake assessments, considering also contemporary consumption habits, are needed to replicate these study’s findings, as the EPIC dietary data were collected in the 1990s, when the consumption of UPFs was still relatively low. As such associations may potentially be stronger in cohorts including recent dietary follow-up assessments.”
Further research is needed to identify other mechanisms, such as food additives and contaminants, which may explain the links observed.
However, based on the finding that body fat did not greatly explain the link between UPF consumption and upper-aerodigestive tract cancer risk in this study, Fernanda Morales-Berstein, suggested: “Focussing solely on weight loss treatment, such as semaglutide, is unlikely to greatly contribute to the prevention of upper-aerodigestive tract cancers related to eating UPFs.”
One of the first studies to look at the association between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality, has found an 85% increase in liver cancer incidence between postmenopausal women who consume one sweetened drink per day and those who consume them rarely. Results from the study, which was led by Brigham and Women’s Hospital, are published in JAMA.
“To our knowledge, this is the first study to report an association between sugar sweetened beverage intake and chronic liver disease mortality,” said first author Longgang Zhao, PhD, of the Brigham’s Channing Division of Network Medicine. Zhao is a postdoctoral researcher who works with senior author Xuehong Zhang, MBBS, ScD, in the Channing Division. “Our findings, if confirmed, may pave the way to a public health strategy to reduce risk of liver disease based on data from a large and geographically diverse cohort.”
This observational study included nearly 100 000 postmenopausal women from the large, prospective Women’s Health Initiative study. Participants reported their usual soft drink, fruit drink (not including fruit juice) consumption, and then reported artificially sweetened beverage consumption after three years. Participants were followed for a median of more than 20 years. Researchers looked at self-reported liver cancer incidence and death due to chronic liver disease such as fibrosis, cirrhosis, or chronic hepatitis, which were further verified by medical records or the National Death Index.
A total of 98 786 postmenopausal women were included in the final analyses. The 6.8% of women who consumed one or more sugar-sweetened beverages daily had an 85% higher risk of liver cancer and 68% higher risk of chronic liver disease mortality compared to those who had fewer than three sugar sweetened beverages per month. No such increase was observed for consumption of artificially-sweetened beverages.
The authors note that the study was observational, and causality cannot be inferred, and relied on self-reported responses about intake, sugar content and outcomes. More studies are needed to validate this risk association and determine why the sugary drinks appeared to increase risk of liver cancer and disease. Furthermore, more research is needed to elucidate the potential mechanisms by integrating genetics, preclinical and experimental studies, and -omics data.
Artificial sweeteners have once again returned to the headlines with the WHO listing them as a possible carcinogen, Now, a long-term study on artificial sweeteners in diets published in the International Journal of Obesity has shown that, ironically, nearly all of them are linked to increased adiposity.
In the two decade long study, University of Minnesota researchers examined people’s regular dietary intake, with a focus on non-nutritive sweeteners commonly found in artificial sweeteners. They found that long-term consumption of aspartame, saccharin and diet beverages were linked to increased abdominal and intramuscular adiposity. However, the study found no significant association between the artificial sweetener sucralose and these measures of fat volume.
“This study showed that habitual, long-term intake of total and individual artificial sweetener intakes are related to greater volumes of adipose tissue, commonly known as body fat,” said Brian Steffen, PhD, MSCR, a professor in the Department of Surgery at the U of M Medical School and co-investigator on the funded grant. “This was found even after accounting for other factors, including how much a person eats or the quality of one’s diet.”
The study’s findings raise concerns about the recommendations from the American Diabetes Association and the American Heart Association that promote the replacement of added sugars with artificial sweeteners. Based on their results, the researchers recommend considering alternative approaches, as long-term artificial sweetener consumption may have potential health consequences.
“This is an especially timely study, given the World Health Organization’s recent warning of the potential health risks of aspartame,” said Lyn Steffen, PhD, MPH, a professor in the School of Public Health and principal investigator on the study. “These findings underscore the importance of finding alternatives to artificial sweeteners in foods and beverages, especially since these added sweeteners may have negative health consequences.”
The researchers say that more studies are needed to better understand the connection between artificial sweetener intake and increased body fat. Further research is warranted to explore the underlying mechanisms and gain clearer insights into how dietary habits affect metabolic health.
A new study published in the Journal of Toxicology and Environmental Health, Part B, found that a chemical formed during the digestion of widely used sweetener is “genotoxic,” meaning it breaks up DNA. The chemical is also found in trace amounts in the sweetener itself, and the finding raises questions about how the sweetener may contribute to health problems.
At issue is sucralose, a widely used artificial sweetener. Previous work by the same research team established that several fat-soluble compounds are produced in the gut after sucralose ingestion. One of these compounds is sucralose-6-acetate.
“Our new work establishes that sucralose-6-acetate is genotoxic,” says Susan Schiffman, corresponding author of the study and an adjunct professor at North Carolina State University. “We also found that trace amounts of sucralose-6-acetate can be found in off-the-shelf sucralose, even before it is consumed and metabolised.
“To put this in context, the European Food Safety Authority has a threshold of toxicological concern for all genotoxic substances of 0.15 micrograms per person per day,” Schiffman says. “Our work suggests that the trace amounts of sucralose-6-acetate in a single, daily sucralose-sweetened drink exceed that threshold. And that’s not even accounting for the amount of sucralose-6-acetate produced as metabolites after people consume sucralose.”
For the study, researchers conducted a series of in vitro experiments exposing human blood cells to sucralose-6-acetate and monitoring for markers of genotoxicity.
“In short, we found that sucralose-6-acetate is genotoxic, and that it effectively broke up DNA in cells that were exposed to the chemical,” Schiffman says.
The researchers also conducted in vitro tests that exposed human gut tissues to sucralose-6-acetate.
“Other studies have found that sucralose can adversely affect gut health, so we wanted to see what might be happening there,” Schiffman says. “When we exposed sucralose and sucralose-6-acetate to gut epithelial tissues – the tissue that lines your gut wall – we found that both chemicals cause ‘leaky gut.’ Basically, they make the wall of the gut more permeable. The chemicals damage the ‘tight junctions,’ or interfaces, where cells in the gut wall connect to each other.
“A leaky gut is problematic, because it means that things that would normally be flushed out of the body in feces are instead leaking out of the gut and being absorbed into the bloodstream.”
The researchers also looked at the genetic activity of the gut cells to see how they responded to the presence of sucralose-6-acetate.
“We found that gut cells exposed to sucralose-6-acetate had increased activity in genes related to oxidative stress, inflammation and carcinogenicity,” Schiffman says.
“This work raises a host of concerns about the potential health effects associated with sucralose and its metabolites. It’s time to revisit the safety and regulatory status of sucralose, because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose. It’s something you should not be eating.”
The World Health Organization (WHO) has released a new guideline on non-sugar sweeteners (NSS), which recommends against using NSS to control body weight or reduce the risk of noncommunicable diseases (NCDs).
This comes as WHO conducts its first review of obesity management guideline in more than two decades. Last week, Francesco Branca, WHO director of nutrition and food safety, had also warned that weight-loss drugs such as Wegovy are “not a silver bullet” in tackling obesity.
The recommendation is based on the findings of a systematic review of the available evidence which suggests that use of NSS does not confer any long-term benefit in reducing body fat in adults or children. Results of the review also suggest that there may be potential undesirable effects from long-term use of NSS, such as an increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults.
“Replacing free sugars with NSS does not help with weight control in the long term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” says Francesco Branca, WHO Director for Nutrition and Food Safety. “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.”
The recommendation applies to all people except individuals with pre-existing diabetes and includes all synthetic and naturally occurring or modified non-nutritive sweeteners that are not classified as sugars found in manufactured foods and beverages, or sold on their own to be added to foods and beverages by consumers. Common NSS include acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, sucralose, stevia and stevia derivatives.
The recommendation does not apply to personal care and hygiene products containing NSS, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols), which are sugars or sugar derivatives containing calories and are therefore not considered NSS.
Because the link observed in the evidence between NSS and disease outcomes might be confounded by baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as conditional, following WHO processes for developing guidelines. This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups.
The WHO guideline on NSS is part of a suite of existing and forthcoming guidelines on healthy diets that aim to establish lifelong healthy eating habits, improve dietary quality and decrease the risk of NCDs worldwide.
Florida State University College of Medicine researchers have linked aspartame, an artificial sweetener found in nearly 5000 diet foods and drinks, to anxiety-like behaviour in mice.
Along with producing anxiety in the mice who consumed aspartame, the effects extended up to two generations from the males exposed to the sweetener. The study is published in the Proceedings of the National Academy of Sciences.
“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.
The study came about, in part, because of previous research from the Bhide Lab on the transgenerational effects of nicotine on mice. The research showed temporary, or epigenetic, changes in mice sperm cells. Unlike genetic changes (mutations), epigenetic changes are reversible and don’t change the DNA sequence; however, they can change how the body reads a DNA sequence.
“We were working on the effects of nicotine on the same type of model,” Bhide said. “The father smokes. What happened to the children?”
Aspartame received FDA approval as a sweetener in 1981. Today, nearly 5000 tonnes are produced each year. When consumed, aspartame becomes aspartic acid, phenylalanine and methanol, all of which can have potent effects on the central nervous system.
Led by doctoral candidate Sara Jones, the study involved providing mice with drinking water containing aspartame at approximately 15% of the FDA-approved maximum daily human intake. The dosage, equivalent to six to eight cans of diet fizzy drink a day for humans, continued for 12 weeks in a study spanning four years.
Pronounced anxiety-like behaviour was observed in the mice through a variety of maze tests across multiple generations descending from the aspartame-exposed males.
“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually you see subtle changes.”
When given diazepam, a drug used to treat anxiety disorder in humans, mice in all generations ceased to show anxiety-like behaviour.
Researchers are planning an additional publication from this study focused on how aspartame affected memory. Future research will identify the molecular mechanisms that influence the transmission of aspartame’s effect across generations.
Since the late 1800s, non-nutritive sweeteners have been used to provide sweetness without sugar. Long been believed to have no effect on the human body, researchers reporting in the journal Cell now challenge this notion by finding that these sugar substitutes are not inert, and, in fact, some can alter human consumers’ microbiomes and thereby their glycaemic responses – albeit in a highly individualised fashion.
Previous research has already found found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycaemic responses, something which the same researchers now investigated in humans.
To address this important question, the research team carefully screened over 1300 individuals for those who strictly avoid non-nutritive sweeteners in their day-to-day lives, and identified a cohort of 120 individuals. These participants were broken into six groups: two controls and four who ingested well below the FDA daily allowances of either aspartame, saccharin, stevia, or sucralose.
“In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secret into peripheral blood. This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners,” said senior author Eran Elinav, an immunologist and microbiome researcher. “When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults. Interestingly, changes in the microbes were highly correlated with the alterations noted in people’s glycaemic responses.”
To prove the microbiomes were responsible, the researchers transferred microbial samples from the study subjects to mice that have been raised in completely sterile conditions, with no microbiome of their own.
“The results were quite striking,” explained Elinav. “In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycaemic alterations that very significantly mirrored those of the donor individuals. In contrast, the bottom responders’ microbiomes were mostly unable to elicit such glycaemic responses,” he added. “These results suggest that the microbiome changes in response to human consumption of non-nutritive sweetener may, at times, induce glycaemic changes in consumers in a highly personalised manner.”
Elinav says that he expects the effects of the sweeteners will vary across individuals because of how unique our microbiomes are. “We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies.”
“In the meantime, we need to continue searching for solutions to our sweet tooth craving, while avoiding sugar, which is clearly most harmful to our metabolic health,” says Elinav. “In my personal view, drinking only water seems to be the best solution.”
