Artificial sweeteners may drive metabolic disease risk
The new research data, published in Nature, investigated the impact of artificial sweetener intake on the make-up of intestinal bacteria and associated changes in metabolism in both animal and human models. Previous research on the topic of artificial sweeteners has been mixed in its findings, with some research pointing to the benefit replacing sugar with low-calorie sweeteners. However, research has also suggested that use of non-calorific sweeteners may be ineffective in battling obesity, and could be associated with an increased risk of metabolic diseases including obesity and diabetes.
Led by Dr Eran Elinav from the Weizmann Institute in Israel, the combined findings suggest that consumption of commonly used non-caloric artificial sweeteners (NAS) could increase the risk of developing glucose intolerance (elevated blood sugar levels) by altering the composition of the microbial ecosystem in our intestines.
"Our relationship with our own individual mix of gut bacteria is a huge factor in determining how the food we eat affects us,” said Elinav. “Especially intriguing is the link between use of artificial sweeteners – through the bacteria in our guts – to a tendency to develop the very disorders they were designed to prevent; this calls for reassessment of today's massive, unsupervised consumption of these substances.”
Mouse findings
Elinav and colleagues gave mice water laced with the three most commonly used artificial sweeteners – saccharin, aspartame and sucralose – at levels equivalent to the maximum permitted by the US FDA. When compared to mice that drank water or sugar water, the team found that these mice developed glucose intolerance.
Repeating the experiment with different types of mice and different doses of the sweeteners produced the same results – suggesting that the non-calorific sweeteners were somehow inducing glucose intolerance, they said.
Next, the team tested the idea that gut bacteria are involved in this phenomenon by treating the mice with antibiotics to eradicate many of their gut bacteria. This resulted in a full reversal of the effects on glucose metabolism, said the authors. Furthermore, they transferred the microbiota from mice that consumed artificial sweeteners to 'germ-free' mice – resulting in a complete transmission of the glucose intolerance into the new mice.
This, in itself, was conclusive proof that changes to the gut bacteria are directly responsible for the harmful effects to their host's metabolism, they said.
Human data
In further assessments on humans the team looked at data collected from their Personalized Nutrition Project, which uncovered a significant association between self-reported consumption of artificial sweeteners, personal configurations of gut bacteria and the propensity for glucose intolerance.
This was followed by a controlled experiment asking a small group of volunteers who did not generally eat or drink artificially sweetened foods to consume them for a week and then undergo tests of their glucose levels as well as their gut microbiota compositions.
Consumption of the artificial sweeteners was found to alter the composition and function of the microbiome in four out of the seven volunteers. These microbial changes had also resulted in metabolic changes that suggested the development of glucose intolerance, said the team.
Implications
The research findings have been met with a mixed response from experts in human nutrition and food, many of whom have questioned the small sample size of the human data and the use of sweeteners at unrealistically levels equivalent to the maximum permitted intake.
Indeed, the data also does against a vast body of science that suggests low-calorie sweeteners are of benefit in weight management because they provide fewer calories than sugar.
“The evidence that the intake of sugared beverages contributes to recent increases in obesity is strong and growing. Recent randomised controlled trials in children have shown that substituting artificially sweetened fizzy drinks for sugared drinks reduces the risks of becoming overweight. This is the background against which the current study needs to be viewed,” commented Professor Sir Stephen O’Rahilly FRS at the University of Cambridge, UK.
O’Rahilly echoed suggestions from other experts that while the findings in mice may suggest a mechanism, the human data from the study “is not compelling as it is seriously underpowered.”
“The human element of this research was only conducted on 7 individuals and this is insufficient to be categorical about firm associations,” added dietician and public health nutritionist Gaynor Bussell. “However, due to the likely increase in NAS use and with what we are beginning to find out about the gut microbiota and metabolic disease I would back the recommendations of the authors to conduct further studies in this area.”
Professor Brian Ratcliffe of Robert Gordon University suggested that the research findings could raise questions about how to best help people lower their intakes of free sugars.
“SACN’s draft recommendations for the UK are in line with WHO’s suggesting that free sugars should be limited to a population average of 5% of dietary energy intake,” said Ratcliffe, citing further recent work that called for targets to be slashed to just 3%.
He also noted that much of the results from the study focus directly to saccharin, and therefore may not apply to other sweeteners that were also studies.
“The study raises some concerns about the widespread use of saccharin and should provoke further investigations,” said Ratcliffe. “The market leaders’ alternatives in the form of ‘diet’ drinks do not usually contain saccharin so there seems no reason to suggest that swapping to a diet version of your favourite fizzy drink is unwise as a strategy to reduce the intake of free sugars.”
Dr John Menzies from the University of Edinburgh added that while the animal data provides a ‘basis’ for a mechanistic explanation of how artificial sweeteners may be involved in metabolic disease, “we do not yet know whether long-term artificial sweetener consumption in humans has the same effects, or whether the amounts of artificial sweeteners consumed in the typical human diet is high enough to put us at risk of metabolic diseases.”
“More work is needed to understand better the metabolic effects of artificial sweeteners,” he said. “But in contrast, the scientific evidence for the contribution of sugar over-consumption to obesity and its associated diseases – diabetes, hypertension and cancer – is very strong.”
“As such, it seems premature to discourage the use of artificial sweeteners in favour of sugar,” said Menzies.
Source: Nature
Published online ahead of print, doi: :10.1038/nature13793
“Artificial sweeteners induce glucose intolerance by altering the gut microbiota”
Authors: Jotham Suez, Tal Korem, et al
