Sweetener combos in food result in irrational metabolic response: Yale study

A greater metabolic response to a sweet-tasting, lower-calorie drink could explain the link between artificial sweetener use and diabetes, according to Yale University scientists.

Writing in the journal Current Biology, the research team point towards the sweet taste as a regulator of metabolic signal generation.

“A calorie is not a calorie,” said senior author Dr Dana Small, professor of psychiatry at Yale University School of Medicine.

“In other words, the assumption that more calories trigger greater metabolic and brain response is wrong,” she added. “Calories are only half of the equation; sweet taste perception is the other half.”

The findings, said the team, have implications for the modern food environment, which offer many energy sources where the sweet taste and carbohydrate co-exist but in “artificial” combinations.

Although some sugar-sweetened beverages are sweetened with only a single sugar, these beverages are in the minority.

For example, Powerade contains glucose, fructose, sucralose, and Acesulfame K while Coca-Cola, Sprite, and Pepsi all contain fructose and glucose. Yogurts also frequently contain multiple varieties of sweeteners.

‘Mismatched conditions’

“Our findings raise the possibility that nutrient partitioning is altered under these mismatched conditions,” the study suggests.

“This suggests a novel mechanism by which sugar-sweetened beverages might negatively influence physiological responses to carbohydrate ingestion.”

Led by Dr Small, four experiments that were partly funded by PepsiCo, were set up to involve a series of neuroimaging and indirect calorimetry human studies.

Here, the relative roles of caloric load and perceived sweetness in driving metabolic, perceptual, and brain responses to sugared beverages were investigated.

In some of the experiments, the caloric load was manipulated using the tasteless carbohydrate maltodextrin, where in others sweetness levels were manipulated using the non-nutritive sweetener sucralose.

By formulating beverages that contain different amounts of maltodextrin and sucralose, the research team was able to demonstrate a non-linear association between caloric load, metabolic response, and reinforcement potency, which is driven in part by the extent to which sweetness is proportional to caloric load.

The mismatch is a characteristic featured in many of today’s processed foods and it is this unfamiliarity that was thought to be driving an irrational response.

“Our bodies evolved to efficiently use the energy sources available in nature,” Dr Small said.

“Our modern food environment is characterized by energy sources our bodies have never seen before.”

The team determined that lower-calorie beverages could produce greater metabolic response and condition greater brain response and liking than higher-calorie beverages.

Additional findings were found when sweetness was proportional to caloric load. Here greater metabolic responses are observed.

“These results demonstrate a non-linear association between caloric load and reward and describe an unanticipated role for sweet taste in regulating carbohydrate metabolism, revealing a novel mechanism by which sugar-sweetened beverages influence physiological responses to carbohydrate ingestion,” the study summarised.

ISA response

Responding to the study, the research does not provide evidence that low cal sweeteners disrupt body metabolism”, the International Sweeteners Association (ISA) stated in a tweet.

"On the contrary, the consumption of the non-caloric beverage led to the expected metabolic responses in the experiments and did not significantly affect glucose and insulin levels nor energy expenditure," they added in a statement.

"Importantly, the collective evidence from well-designed intervention studies repetitively shows that low calorie sweeteners can help in reducing energy intake and in weight loss, when used in place of sugar and as part of a healthy diet.”

In a newly published booklet entitled: ‘Low calorie sweeteners: Insights into their use, benefits and role in a healthy diet', ISA pointed to human studies that showed the use of low-calorie sweeteners did not affect blood glucose levels in both healthy individuals and people with diabetes.

“In a systematic review summarising the available randomised clinical trials (RCTs) in the scientific literature, the vast majority of clinical studies confirmed that the different low calorie sweeteners do not affect glycaemic indexes such as blood glucose, insulin secretion or glycosylated hemoglobin (Hb1Ac)."

This same conclusion was also reached in an earlier systematic review evaluating the impact of diet composition on blood glucose regulation.

Source: Current Biology

Published online ahead of print: doi.org/10.1016/j.cub.2017.07.018

“Integration of Sweet Taste and Metabolism Determines Carbohydrate Reward”

Authors: Dana Small et al.