March 28, 2024

expert reaction to study looking at sweeteners and appetite

A study published in eBioMedicine looks at sweeteners and appetite in obese adults. 

Prof Kevin McConway, Emeritus Professor of Applied Statistics, Open University, said:

“This is generally a well-designed and well-executed trial in statistical terms.  In a way, though, it provides a good example of how complicated it is to sort out the different possible effects of artificial sweeteners, and how there’s still a great deal to learn about how they might affect human bodies.

“It’s good that this study used solid foods (biscuits, in fact), because so many studies and discussions of artificial sweeteners have concentrated on drinks.  It’s good that each participant ate all of the three types of biscuit used (one with sugar, the other two with different non-sugar sweeteners), because that allows comparisons of how the same person reacts to different biscuit types.  If instead each person had eaten only one type of biscuit, any differences between the effects of the biscuits might have been obscured by differences between participants.  It’s good that each person ate each biscuit type daily for as long as two weeks, rather than everything being based on just one or two biscuit-eating sessions.

“But it’s important to understand what the results can tell us.  There are some limitations.

“Two weeks of consumption is a lot better than just one day, but it’s still not all that long and maybe some other differences would have showed up if it had been possible for people to continue eating the biscuits for a lot longer.  However, given all the measurements had to be made on the participants, and the demands on their time, it just wouldn’t be practicable to continue a trial like this for much longer.

“The researchers point out another limitation, or perhaps more precisely, something that it’s important to be clear about in understanding what was investigated in the study.  They weren’t simply comparing biscuits containing sugar with biscuits that had one or other of the two sweeteners being investigated in place of the sugar.  The non-sugar biscuits also contained substances called polyols (specifically, mannitol and sorbitol).  These substances are quite commonly used in products without added sugars, and the researchers explain that they had to use them here in order to match the sugar-containing biscuits and the others reasonably well in terms of calorie content, taste, and feel.  In a trial like this, it’s important for many reasons that the things being compared are as similar as possible, except in terms of the actual substances being compared.  For instance, without matching the biscuits as well possible, if the non-sugar biscuits had tasted or felt very different from the sugary ones, the participants might well have clearly guessed which were which and that could have changed what they reported about their appetites and so on after eating them, for reasons not directly to do with the sweeteners.

“But this does mean that what’s actually being compared is the effects of eating biscuits containing sugar, with eating biscuits containing one of the two sweeteners together with quite a lot of mannitol and sorbitol.  So any specific effects of one or other of the sweeteners can’t be separated out from any effects of the polyols (mannitol and sorbitol) on the appetite measure or other measurements.  That certainly doesn’t mean that the trial was useless for its stated purpose – just that we need to be a bit careful about what it does imply.

“In the Introduction of their research paper, the researchers draw attention to the 2023 WHO Guideline on the use of non-sugar sweeteners¹, which made a conditional recommendation: “WHO suggests that non-sugar sweeteners not be used as a means of achieving weight control or reducing the risk of noncommunicable diseases.”  That recommendation was controversial, and it was conditional and expressed only as a suggestion.  It was based partly on data from randomized clinical trials (RCTs), like this new research, but also on data from observational studies, and the suggestions that non-sugar sweeteners might not help with weight control or reducing disease risk came predominantly from the observational studies.  Observational studies always have problems in determining what causes what, and they usually don’t throw much light on the actual mechanisms by which (in this case) artificial sweeteners might work inside the body.

“This new trial exemplifies that RCTs can throw some light on what goes on in the body, and can provide answers to some questions about cause and effect, but they are elaborate, specific, usually expensive, and can’t generally look at long-term effects.  This one, for instance, can’t really tell us anything about effects of sweeteners on weight control, and wasn’t intended to do so, so it says little about the WHO recommendation on sweeteners and weight control.  (In any case the different types of biscuit were reasonably closely matched in terms of their calorie content, though the biscuits containing the non-sugar sweeteners and polyols did contain about 9% fewer calories.)

“So, at present, there isn’t a practicable alternative to using observational studies to investigate long-term effects, including long-term risks of disease, despite their inevitable shortcomings.  It’s true that the review of research behind the WHO guideline² generally rated confidence in the long-term findings as low, but that’s primarily because those findings came from observational studies.  It’s not that the observational studies were all poor studies of their type – only that any observational study has important limitations.”

1 https://www.who.int/publications/i/item/9789240073616

2 https://www.who.int/publications/i/item/9789240046429

*UPDATED COMMENT* Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:

“This study examined the effects of biscuits reformulated with combination of polyols and intense sweeteners (Neotame or Stevia) compared with control biscuits that had a higher sugar content.  The main outcome was a composite score of the effect on appetite in three hours following consumption.  The study found no differences between treatments compared with control in this outcome but it did find smaller increases in blood insulin levels following consumption of the biscuits compared with the control, which would be expected because about 20 g of the sugar content in the control was replaced with polyols.

“Polyols are sugar alcohols that are not digested in the small bowel but can be fermented in the gut.  However, consumption of more than 25 g polyols can result in osmotic diarrhoea so the practicality of using this type of reformulation, which reduced calorie intake by 34 kcal for 3 biscuits, is questionable especially as they would need to carry the health warning “Excessive consumption may produce laxative effects”.  The reformulated biscuits also provided a higher proportion of energy from fat.”

Prof Keith Frayn, Emeritus Professor of Human Metabolism, University of Oxford, said:

“This study reports sensations of appetite during the 3-hour period after eating three biscuits which were sweetened with either table sugar or one of two different low-calorie (non-sugar) sweeteners.  The authors report no differences in feelings of appetite between the different types of biscuit.  In the Press Release they suggest that the findings provide “crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control”.  This would be important as the World Health Organisation in 2023 argued that artificial sweeteners are not to be recommended for weight control due to lack of evidence that they were beneficial in longer-term studies.

“But the findings of this paper are not particularly surprising.  There was more fibre – which aids the feeling of fullness – in the biscuits with the sweeteners.  The finding of a lower blood glucose and insulin response is hardly a surprise given that the ‘table sugar biscuits’ provided 21 grammes of sugar, half of which will be glucose, whereas the biscuits with sweeteners contained less than 2 grammes.  It is difficult to see new lessons here for people with diabetes.  This study would need to be extended over a much longer period before we could deduce anything about effects on body weight and glucose control.  The study does highlight a difficulty in replacing sugar in food products: sugar is more than a sweetener, it improves the texture of food.  These researchers had to mimic that by adding polyols (sugar alcohols) to the biscuits with the non-sugar sweeteners, which may be the reason that some volunteers had intestinal problems after eating these biscuits.”

Dr Duane Mellor, Registered Dietitian and Senior Lecturer, Aston Medical School, Aston University, said:

“Although this study looks on the surface to be promising in that people who were living with overweight or obesity, when given three biscuits containing sweeteners (one group given stevia (a plant derived sweetener), one given neotame (an artificial sweetener), compared to a group given sucrose (sugar sweetened)) found that eating biscuits containing sweeteners had no negative effects on self-reported appetite measures or appetite related hormones.  This came with the potential benefit, in that those who ate the sweetener-containing biscuits had lower blood glucose (sugar) levels and insulin levels (the hormone that controls blood glucose) in the three hours after eating the biscuits.

“However, these are not low calorie alternatives at 109 kcal per biscuit (which were specially developed for this research and are not currently available in the shops) for the sweetened biscuits (compared to 120kcal per biscuit for the control) – these are unlikely to be a positive contribution to help an individual manage or lose weight.

“Additionally, due to technical challenges with developing a biscuit that contains a sweetener instead of sugar, the physical properties of sugar required polyols (also known as sugar alcohols) to be used as a bulk replacement for sugar as the sweeteners are only needed in tiny amounts.  The level of polyols in the biscuits was nearly 23%.  Any food that contains more than 10% polyols that is sold in the UK has to carry a warning ‘excessive consumption may have a laxative effect’.  Polyols were historically used in what were called ‘diabetic foods’, but they fell out of favour due to this laxative effect and that they were still high in energy (calories).  In this study, individuals who had the sweetener-containing biscuits reported more digestive symptoms (although most participants did not link them to eating the biscuits).  Therefore, although this study suggested a metabolic benefit of these biscuits, due to their calorie content and issues with the potentially diarrhoea-causing polyols they contain, they are unlikely to find their way to supermarket shelves soon!”

‘Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity—a randomised crossover trial from the SWEET consortium’ by Catherine Gibbons et al. was published in eBioMedicine at 23:30 UK time on Thursday 28 March 2024. 

DOI: 10.1016/j.ebiom.2024.105005

Declared interests

Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee.  My quote above is in my capacity as an independent professional statistician.”

Prof Tom Sanders: “Member of the Science Committee British Nutrition Foundation.  Honorary Nutritional Director HEART UK.

Before my retirement from King’s College London in 2014, I acted as a consultant to many companies and organisations involved in the manufacture of what are now designated ultraprocessed foods.

I used to be a consultant to the Breakfast Cereals Advisory Board of the Food and Drink Federation.

I used to be a consultant for aspartame more than a decade ago.

When I was doing research at King’ College London, the following applied: Tom does not hold any grants or have any consultancies with companies involved in the production or marketing of sugar-sweetened drinks.  In reference to previous funding to Tom’s institution: £4.5 million was donated to King’s College London by Tate & Lyle in 2006; this funding finished in 2011. This money was given to the College and was in recognition of the discovery of the artificial sweetener sucralose by Prof Hough at the Queen Elizabeth College (QEC), which merged with King’s College London. The Tate & Lyle grant paid for the Clinical Research Centre at St Thomas’ that is run by the Guy’s & St Thomas’ Trust, it was not used to fund research on sugar. Tate & Lyle sold their sugar interests to American Sugar so the brand Tate & Lyle still exists but it is no longer linked to the company Tate & Lyle PLC, which gave the money to King’s College London in 2006.”

Prof Keith Frayn: “I have no conflict of interest to declare other than as an author of books on metabolism and body weight.”

Dr Duane Mellor: “Duane Mellor has previously worked with the International Sweetener Association.”