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Non-nutritive sweeteners linked to heart disease and cancer

Results of recent studies on non-sugar sweeteners are a dramatic departure from decades of received public health wisdom advocating replacing sugar with sugar substitutes.

Nutritionists have found that although these help with weight management in the short term, in the long term, they are linked to higher risk of obesity, type 2 diabetes, cardiovascular diseases and higher body-mass index.

Since the introduction of the Health Promotion Levy in 2018 (the so-called “sugar tax”), the use of “non-nutritive sweeteners” in South African drinks has exploded, as it has in more than 50 other countries that have introduced similar taxes.

Non-nutritive sweeteners have little to no nutritional value, are mostly made of chemicals (with a few plant-based exceptions), and are often much sweeter – gram for gram – than sugar, reports the Daily Maverick.

Worldwide, governments’ rationale for introducing sugar taxes has been to protect public health: Sugary drinks consumption, even more than sugary foods, has been proven to be a major driver of obesity, type 2 diabetes and other life-threatening, non-communicable diseases like cardiovascular disease and some cancers.

About one in eight South African adults is diabetic: 31% of men, 68% of women and 13.5% of children are overweight or obese.

Around 12m people in this country have weight-related diseases for which they receive treatment in the public sector, and these include diabetes, hypertension, cardiovascular disease, arthritis and cancer.

In SA, the tax of 2.1 cents is levied on every gram of sugar above 4g per 100ml, and is paid by the manufacturer to SARS. (To compare: “Original Taste” Coca-Cola contains 10.6g of sugar per 100ml.) On average, the price of carbonated drinks increased by just more than R1 per litre because of the tax, passing the increase on to the consumer.

But instead of simply making the drinks less sweet, manufacturers have replaced some of the sugar they’ve removed with non-nutritive sweeteners.

A typical nutrition-information label on a can of a sugary drink is likely to include sugar, aspartame, acesulfame-K (potassium) and sucralose or cyclamates. Aspartame alone is used in more than 6 000 processed foods and drinks globally, including Diet Coke, Coke Zero and Diet Pepsi.

In South Africa, since 2018, non-nutritive sweeteners show up even where you don’t expect them, like in a “normal”, still partly sugar-sweetened tonic water or ginger ale. This is because the tax has had the intended effect: to incentivise manufacturers to reduce the quantity of sugar in all their drinks.

The history of ‘artificial’ sweeteners

Non-nutritive sweeteners have generally been considered (and marketed, as the World Health Organisation points out) as one means of blood sugar/glucose control in people with diabetes.

Saccharin, publicised in 1893 as a “perfectly harmless spice” 500 times sweeter than “the best sugar”, was the first in a series of “miraculous” discoveries of substances sweeter than sugar, but allegedly without sugar’s harmful effects.

In 1977, the US Food and Drug Administration (FDA) tried but failed to ban saccharin after clinical studies showed consuming large amounts of it caused bladder cancer in rats. (This result was controversial, given the huge quantities of saccharin given to the rats in the trial.)

Saccharin (sold commercially as Sweet ’n Low) was largely overtaken first by cyclamate in the 1930s (also linked to bladder cancer in rats, and banned in the US by the FDA in 1969), and later by new generations of sweeteners, used in an array of products from soft drinks to salad dressings to effervescent vitamin supplements.

They include aspartame (marketed as Equal and NutraSweet), sucralose (Splenda), acesulfame-K, xylitol, mannitol, sorbitol and other sugar-alcohol (or “polyol-”) derived sweeteners.

More recently, the plant-derived stevia and monk fruit are on the rise as sweet alternatives to sugar.

Since the early 2000s, aspartame has come under a cloud of safety scares after several research studies from Italy showed it caused malignant tumours in rats and mice. But in 2013, the European Food Safety Agency said aspartame was safe for the general population.

New science, and WHO, raise the alarm about sweeteners

Because of the recent global rise of sugar taxes, and as a result of the increased use of non-nutritive sweeteners in foods and drinks, the WHO performed a “systematic review” – an analysis of all available scientific literature on a topic – of “non-sugar sweeteners”, to properly understand whether their benefits are all they’re boasted to be in reducing sugar consumption, and the associated risks to human health.

The results are a dramatic departure from decades of received public health wisdom that advocated for replacing sugar with sugar substitutes which, it was thought, had no effect on blood sugar.

Alarming nutritionists, as well as manufacturers of non-sugar sweeteners, is the finding that although sugar substitutes help with weight management in the short term, in the long term they are associated with increased risk of obesity, type 2 diabetes, body-mass index and cardiovascular diseases.

In July 2022, the WHO published draft guidelines on non-sugar sweeteners, based on the review’s results. The draft guidelines completely upended previous recommendations, stating:

“WHO suggests that NSS (non-sugar sweeteners) not be used as a means of achieving weight control or reducing risk of non-communicable diseases”.

Further, the draft guidelines focus on the broad “health effects” of non-sugar sweeteners, food writer Bee Wilson has emphasised, especially long-term weight gain and the observed increased risk of type 2 diabetes.

Corroborating research

Since then, two other pieces of recent research corroborate the WHO’s advice.

In September 2022, a French study of more than 103 000 adults showed that heavy use of non-nutritive sweeteners is linked to increased risk of cardiovascular, cerebrovascular and coronary heart disease.

The research, published in the British Medical Journal, stated: “Our results indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies.”

In August 2022, researchers led by Professor Eran Elinav, an immunologist at Israel’s Weizmann Institute of Science, conducted a randomised controlled trial looking at the blood sugar and metabolic effects of four different non-nutritive sweeteners (aspartame, stevia, sucralose and saccharin) using six groups of trial volunteers. (Elinav and team had done a similar study in 2014 showing that non-nutritive sweeteners affected the microbiomes of mice; this is the first such study among humans.)

Participants in each of four groups ingested one of the sweeteners, while the fifth and sixth groups acted as “control groups”, to allow researchers to compare the effects on blood sugar of the sweeteners vs sugar, or nothing. The fifth group ingested just a sachet of glucose; the sixth group ingested nothing.

The results, published in the scientific journal Cell, were alarming: All four sweeteners caused changes to the gut microbiome.

“In subjects consuming the non-nutritive sweeteners,” Erinav reported, “we could identify very distinct changes in the composition and function of gut microbes and the molecules they secrete into peripheral blood… suggesting gut microbes are rather responsive to each of these sweeteners.”

In addition, while stevia and aspartame had no discernible effects on blood sugar, saccharin and sucralose “significantly impacted glucose tolerance in healthy adults”, in other words, raised the blood sugar of trial participants. (In the sucralose group, participants experienced varied blood sugar, or “glycaemic”, responses).

Elinav said the changes in the gut bacteria were “highly correlated” with the changes noted in people’s glycaemic responses. This is important because the gut microbiome is increasingly being understood to influence each of our risk factors for obesity, type 2 diabetes and heart disease. And our gut microbiomes are in turn influenced by what we eat.

As the UK’s Dr Tim Spector describes it, when you feed yourself, you are also feeding your gut microbiome (which weighs more than your brain, incidentally: around 2kg).

Spector, a professor of genetic epidemiology at King’s College London, leads a groundbreaking, ongoing research project on individual human responses to food (the world’s largest), called PREDICT (Personalised Responses to Dietary Composition Trial), which began in the UK in 2018, with a cohort of almost 1 100 adults.

In 2021, research results analysing participants’ hormones, cholesterol, blood sugar and inflammation levels showed microbiomes are largely shaped by what they eat (identical twins, for example, share only 34% of the same gut microbes).

The results came from blood tests before and after meals, two weeks of continuous glucose monitoring, and tracking of sleep and physical activity. The types of bacteria present in each individual’s microbiome “played a strong role in their metabolic health”.

Eating a large proportion of highly processed foods, including excessive amounts of salt, sugar and unhealthy fats, preservatives and additives, is linked to much higher risk of poor metabolic and heart health, compared to eating a high proportion of whole, relatively unprocessed and fresh foods including high-fibre plants, which support the growth of good bacteria in the gut.

The bottom line is that none passes through us without affecting blood-sugar-related aspects of how we function, as previously thought.

What this means for South Africa

South Africa’s four-year-old sugar tax has been considered successful so far, in that consumers have bought fewer carbonated drinks (29% fewer in urban areas) and the sugar in those drinks has been cut back by half (51%).

In addition, the change was even greater among lower socioeconomic groups. This is good news in terms of long-term benefits from cutting down on sugar: science has shown that drinking even one sugary drink a day increases an adult’s likelihood of being overweight by 27%, and a child’s by 55%.

However, the new WHO draft guidelines and other recent research calls an element of this success into question. Are the non-nutritive sweeteners now replacing sugar actually benefiting our health, or causing even greater or different damage to our long-term health because of the influence of sweeteners on our glycaemic responses and on our gut microbiomes?

As with many other food-related regulations, South Africa has no updated regulations on the use of non-nutritive sweeteners.

The regulation that does exist is 2012’s R733, Regulations for the use of sweeteners in foods, which says: “Sweeteners may not be used in foods intended for infants and young children”, but there are no corresponding warnings on foods containing non-sugar sweeteners that they should not be given to young children.

It remains to be seen whether the much-anticipated front-of-pack warning labels that the Department of Health is expected to unveil soon will include cautionary guidance on the use of sweeteners, particularly for children, in line with the imminent WHO draft guidelines.

That sugar-sweetened beverages – all carbonated drinks, including ginger ale, tonic water and energy drinks – now contain sugar and non-nutritive sweeteners, may mean the well-intentioned reformulation of drinks to lower their sugar content might come back to bite us.

The negative impacts of continued consumption of sweetened drinks on our blood sugar, our gut microbiomes and on our taste preference, nurturing our palates to want ever-sweeter foods and beverages, might be setting us up for various harmful long-term effects from non-nutritive sweeteners, including long-term weight gain and elevated risk for diabetes, two of the very problems from which they were intended to save us.

The WHO draft guidelines on non-sugar sweeteners suggest that eating more “minimally processed unsweetened foods and beverages” would be preferable to replacing sugar with sweeteners, in foods and drinks.

In South Africa, however, where schools often don’t have clean drinking water, but have tuck shops selling sugar-sweetened beverage, and where supermarkets sell a 2-litre sugary drink for less than the same quantity of bottled water, persuading children and adults of the benefits of drinking only water presents challenges that cannot be addressed by simply targeting individuals’ “choice” of what to drink.

Note: Dr Jason Montez, a scientist in the WHO’s Department of Nutrition and Food Safety, told Maverick Citizen that the WHO aims to release the final guideline on the use of non-sugar sweeteners in April 2023.

CELL Study details

Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance

Jotham Suez, Yotam Cohen, Rafael Valdés-Mas, Christoph K. Stein-Thoeringer, Eran Segal, Eran Elinav et al.

Published in Cell on 19 August 2022

• Randomised-controlled trial on the effects of non-nutritive sweeteners in humans
• Sucralose and saccharin supplementation impairs glycemic response in healthy adults
• Personalised effects of non-nutritive sweeteners on microbiome and metabolome
• Impacts on the microbiome are causally linked to elevated glycemic response

Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycaemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomised-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycaemic responses. Importantly, gnotobiotic mice conventionalised with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycaemic responses largely reflecting those noted in respective human donors, which were pre-empted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycaemic alterations, necessitating future assessment of clinical implications.


regulations sweeteners

Cell article – Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance (Open access)


Nature PREDICT Trial article – Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals (Open access)


Daily Maverick article – Growing medical evidence shows non-nutritive sweeteners, widely used in drinks and food, sabotage health (Open access)


See more from MedicalBrief archives:


Study contradicts earlier findings on saccharin-for-sugar substitution and diabetes


Artificial sweeteners’ link to higher risk of heart disease – French study


Artificial sweeteners and increased cancer risk – French cohort study


Sugar tax has cut consumption of sugary drinks — meta-analysis


Artificial sweeteners may leave a bitter aftertaste





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