Sweeteners during pregnancy may increase obesity risk in offspring

17 Jan 2022 --- Consuming sweeteners during pregnancy could put children more at risk of obesity via changes to their microbiome, despite these changes not occurring in the mother. 

This was the conclusion of a Canada-based study that determined “intense sweet tastants have a lasting and intergenerational effect on gut microbiota and host health” in rats.

“Low-calorie sweeteners are largely non-toxic to adults. But they may have some unexpected effects in pregnancy,” Dr. Weilan Wang, first author on the study, tells NutritionInsight. 

Microbes linked to higher fat percentage 
Rat pups born to mothers fed either aspartame or stevia had a higher body fat percentage and notable changes in their gut microbial communities compared to the control group who received water rather than a sweetener. 

Both aspartame and stevia were used to represent artificial and natural low-calorie sweeteners. 

The Food Directorate of Health Canada deems up to 4 mg of stevia per 1 kg of body weight per day an acceptable daily intake.Namely, the pups with extra weight gain had increases in propionate- and butyrate-producing microbes and reductions in lactose-fermenting species.

“Production of the short-chain fatty acids propionate and butyrate in the intestine have received particular attention for their roles in intestinal homeostasis and energy metabolism,” says Wang. 

“We showed a positive correlation between these microbes and higher body weight gain and body fat in our study.”

Dosed to replicate human consumption 
The doses were created to reflect what humans might typically consume, says Wang, and they were well within the acceptable daily intake levels. 

Pregnant rats received either 5 to 7 mg/kg body weight of aspartame or 2-3 mg/kg body weight of stevia per day.

This compares to 40 mg/kg of aspartame and 4 mg/kg of stevia deemed as safe by the Food Directorate of Health Canada. 

A healthier option? 
Low-calorie sweeteners are considered by many to be a healthier alternative to sugar because of their lower calorie content, states Wang. 

Nutritional advocacy groups, such as Action on Sugar, have long called for reformulation to lower the sugar content in F&B, such as children’s food in the UK.

However, Wang notes that this is not the first study to suggest prenatal consumption by mothers can affect obesity risk in infants.

“Ultimately, we hope to identify the mechanism or pathway by which maternal aspartame and stevia consumption exert effects on offspring that never directly consumed the sweeteners themselves.”

A section of a mouse small intestine shows neuropod cells in green and sodium glucose transporter 1 in yellow, responsible for communicating the presence of sugar in the gut to the brain (Credit: Diego Bohorquez Lab, Duke University). Are the findings valid in humans?
While the research was conducted on animals, Wang says the findings could have important implications for human health. 

“The diet of human mothers during pregnancy and lactation likely also impacts the gut microbiota, microbial metabolites and the metabolic fitness of their children.”

Dr. Raylene Reimer, senior author on the Canadian study asserts that confirming the findings [of intergenerational effects of sweeteners] in humans is very important. A study with thousands of mother-child pairs is currently underway, she says, with results expected later this year. 

The human study will investigate the body weight and obesity risk of children whose mothers consumed diet soft drinks during pregnancy.

Getting a sense of sugar 
There is still much to learn on how sugar and sweeteners are sensed and processed, and the gut’s role in it. 

In an unrelated study, researchers at Duke University noticed that mice consistently prefer real natural sugar to artificial sweeteners – even if their taste buds have been knocked out. 

Researcher Kelly Buchanan, lead author on the study, says that mice’s preference for real sugar is regulated by the gut and attributed to neuropod cells found in the upper small intestines. 

“Both sugars and sweeteners excite neuropod cells in our guts that communicate to the brain using different signaling molecules,” explains Buchanan. 

The difference is, the consumption of sugar triggers gut glutamate as a neurotransmitter, but sweeteners trigger the release of a different molecule, ATP. 

“What information ATP communicates to the brain and how it regulates our behavior is a fascinating question for future studies,” says Buchanan. 

Interestingly, when neuropod cells in mice were knocked out – mice no longer preferred regular sugar over sweeteners. 

The researcher write that that the presence of these sugar-sensing cells could help researchers understand why artificial sweeteners don’t curb sugar cravings.

Sugar alternatives gain ground
Sweeteners are increasingly popular in food and beverage formulation, featuring a +3% year-over-year growth when comparing 2020 and 2021 launches, according to Innova Market Insights. 

A 2020 report publicized by the International Sweeteners Association (ISA) argued that there is an extensive body of robust scientific evidence that shows that low- and no-calorie sweeteners are safe and can be part of broader strategies to reduce sugar intake.

Nevertheless, some studies continue to question low-calorie sweeteners’ ability to prevent obesity, such as a study last September that suggested sucralose may increase cravings. 

A study the same year raised concerns that stevia could disrupt quorum sensing (bacterial communication) in the gut leading to a microbial imbalance. 

By Missy Green