Thursday September 18 2014
Artificial sweeteners have courted controversy recently
"Artificial sweeteners may promote diabetes, claim scientists," reports The Guardian. But before you go clearing your fridge of diet colas, the research in question – extensive as it was – was mainly in mice.
The researchers' experiments suggest artificial sweeteners, particularly saccharin, change the bacteria that normally live in the gut and help to digest nutrients.
These changes could reduce the body's ability to deal with sugar, leading to glucose intolerance, which can be an early warning sign of type 2 diabetes.
Assessments in human volunteers suggested the findings might also apply to people. But human studies so far are limited.
The researchers only directly tested the effect of saccharin in an uncontrolled study on just seven healthy adults over the course of a week. It is far too early to claim with any confidence that artificial sweeteners could be contributing to the diabetes "epidemic".
In the interim, if you are trying to reduce your sugar intake to control your weight or diabetes, you can always try to do so without using artificial sweeteners. For example, drinking tap water is a far cheaper alternative to diet drinks.
Where did the study come from?
This study was carried out by researchers at the Weizmann Institute of Science and other research centres in Israel.
It was funded by the Weizmann Institute and the Nancy and Stephen Grand Israel National Center for Personalized Medicine, as well as grants from various research funders globally.
The study was published in the peer-reviewed medical journal Nature.
The Guardian covered this study well, avoiding sensationalising the results. The paper and other media outlets, including the Daily Mail, included balanced quotes from various experts that highlight the study's limitations.
However, The Guardian reports the daily amount of saccharin used in the study in humans "was enough to sweeten around 40 cans of diet cola", but it is unclear where this estimate came from. Saccharin is not commonly used in diet drinks any longer, with aspartame being the preferred choice of most manufacturers.
The Daily Express only included quotes from the study author (for) and a representative of the British Soft Drinks Association (against), which – as you would expect – polarised the debate.
What kind of research was this?
This was animal and human research looking at the effect of artificial sweeteners on bacteria in the gut and how this influences glucose metabolism.
Animal research is often one of the first steps in investigating theories about the biological effects of substances. It allows researchers to carry out studies that could not be done in humans.
Because of differences between species, results in animals may not always reflect what happens in humans, but they allow researchers to develop a better idea of how things might work.
They can then use this knowledge to develop ways to test their theories using information that can be obtained in humans. This study has carried out both the animal and early human tests of their theories. But the human part of this study was relatively limited, as the focus was on the animal research.
The researchers carried out a cross-sectional analysis of artificial sweetener exposure and indicators of metabolic problems and gut bacteria. This approach is not able to determine whether the sweetener could be contributing to the outcomes seen, or vice versa.
The researchers also tested the short-term effect of saccharin on people who never consumed the sweetener, but without a control group.
What did the research involve?
The researchers compared the effect of consuming the artificial sweeteners against water, glucose and sucrose on glucose tolerance in lean mice and obese mice (mice eating a high-fat diet). Glucose tolerance testing assesses how quickly the body can clear glucose from the blood after glucose is eaten.
The body normally responds by quickly taking glucose up into cells for use and storage. If the body is slow to do this, this is called glucose intolerance. Very high glucose intolerance in humans indicates diabetes.
The researchers carried out various experiments to test whether the changes seen might relate to the artificial sweeteners having an effect on the bacteria in the gut, and exactly what these effects were.
They then carried out tests to see whether artificial sweetener consumption could have similar effects in humans. They did this by cross-sectionally assessing long-term artificial sweetener consumption and various indicators of glucose metabolism problems in a sample of 381 people who were not diabetic.
They also tested the effects of commercial saccharin given to seven healthy adult volunteers who did not normally consume saccharin. This was given over the course of six days at the US Food and Drug Agency's (FDA) maximum acceptable level (5mg per kg body weight), equivalent to 120mg a day.
What were the basic results?
The researchers found both lean and obese mice consuming the artificial sweeteners saccharin, sucralose or aspartame in their water over 11 weeks developed glucose intolerance, while those consuming just water, glucose or sucrose did not.
Saccharin had the greatest effect on glucose intolerance, and the researchers focused most of their experiments on this sweetener. It caused glucose intolerance within five weeks when given at a dose equivalent to the US Food and Drug Administration (FDA) maximum acceptable daily intake in humans.
The researchers found the mice consuming the artificial sweeteners did not differ in their liquid and food consumption or their walking and energy expenditure compared with the controls. These factors were therefore considered to not be causing the glucose intolerance.
However, treating mice with antibiotics stopped the artificial sweeteners having this effect. Mice with no gut bacteria developed glucose intolerance when the researchers transplanted gut bacteria taken from mice consuming saccharin or being treated with saccharin in the lab. These results suggest the sweeteners were having some effect on the gut bacteria, which was causing the glucose intolerance.
The researchers also found drinking saccharin changed the types of bacteria in the mice's guts. Drinking water, glucose or sucrose did not have this effect.
The bacteria in the gut are involved in helping to digest nutrients. The specific changes seen in mice consuming saccharin suggest the sweeteners could be increasing the amount of energy that could be harvested from these nutrients.
In their human studies, the researchers found:
- Long-term artificial sweetener consumption in 381 people who were not diabetic was associated with greater waist circumference, waist to hip ratio, levels of glucose in the blood after fasting, and worse glucose tolerance.
- People who consumed artificial sweeteners had a different gut bacteria composition from people who did not consume artificial sweeteners.
- Four out of seven healthy adult volunteers who did not normally consume artificial sweeteners developed worse glucose tolerance after consuming the maximum US FDA-recommended level of saccharin for six days. These four people showed gut bacteria differences compared with the three people who did not show an effect, both before and after consuming the saccharin.
- Transfer of gut bacteria from the volunteers showing a response to bacteria-free mice caused the mice to develop glucose intolerance. This was not seen if they transferred gut bacteria from the non-responding human volunteers to mice.
How did the researchers interpret the results?
The researchers concluded that consuming artificial sweeteners increases the risk of glucose intolerance in mice and humans by changing the gut bacteria and therefore affecting their function.
They say their findings suggest artificial sweeteners "may have directly contributed to enhancing the exact epidemic [obesity and diabetes] that they themselves were intended to fight".
This fascinating and controversial study in mice and humans suggests artificial sweeteners, particularly saccharin, could lead to glucose intolerance by having an effect on gut bacteria. The fact that both the animal and human experiments seem to support this adds some weight to the findings.
However, the researchers' investigations in humans are currently limited. They assessed the link between long-term artificial sweetener consumption and various indicators of metabolic problems, such as fat around the waist, using a cross-sectional design. This cannot establish which came first and therefore which could be influencing the other. Also, the only confounder in humans that seemed to be considered was body mass index.
The researchers also only directly tested the effect of one artificial sweetener (saccharin) in an uncontrolled study on just seven healthy adults over the course of a week. Saccharin is less commonly used than other artificial sweeteners, and the participants also consumed it at the maximum US FDA-recommended level (equivalent to 120mg a day).
The findings suggest – at least in the short term – saccharin may only affect glucose response in some people, depending on their gut bacteria. Larger studies, which also incorporate a control group, are needed to see whether they support the results and whether other sweeteners have similar effects.
Some earlier human studies have found links between artificial sweeteners and weight gain and increased diabetes risk. However, it has generally been assumed this is because the people who consume more artificial sweeteners because the sweeteners contain no calories already have problems with their weight, which is why they are at more risk, not vice versa (reverse causation).
This study raises the intriguing possibility that artificial sweeteners could also be directly affecting how our bodies respond to sugar. However, this research is only in its early stages, and we cannot say for certain whether artificial sweeteners are contributing to the diabetes epidemic.
In the interim, if you are trying to reduce your sugar intake, you can do so without replacing sugar with artificial sweeteners.
For people trying to lose weight and those with diabetes who are trying to control their blood sugar, it is important to do what works for them as this is more likely to be sustainable in the long term.
For some people, substituting food and drinks containing artificial sweeteners, rather than those containing sugar, may help with these goals.
At this stage, it is far too early to drop artificial sweeteners from the arsenal of sugar alternatives that could be used to fight the diabetes and obesity epidemic.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.