Are sugar substitutes healthier than the real thing?

The promise of sugar substitutes is simple: found in everything from yogurts to toothpaste, they claim to let people gorge on sweet treats without piling on weight and the tooth decay caused by sugar-loving bacteria. Now a growing body of research is suggesting that these substances may have surprisingly bitter consequences.

Sugar substitutes are a mixed sachet. They include synthetic concoctions (such as aspartame, saccharin and sucralose) and substances derived from plants, including a family of carbohydrates known as sugar alcohols (such as erythritol, maltitol, sorbitol and xylitol) and stevia. Some strike the human tongue as hundreds of times sweeter than sugar, so are added in tiny amounts to foods and drinks. These small quantities, combined with the observation that many are excreted largely unchanged, have led to the assumption that they pass through the human body without affecting metabolism.

Things may not be so simple. In some randomised controlled trials (typically lasting 4-12 weeks) substituting other sweeteners for sugars did admittedly result in lower weight gain. But a number of large, long-term observational studies have found the opposite: people with higher consumption of sugar substitutes—some of whom may be using these to replace sugar in their diets—end up putting on more weight than those who consume the least. Other studies show that they also end up with higher rates of heart problems, diabetes and cancer than abstainers.

Proving causality through such observational studies is difficult, as it would involve accounting for all the ways in which people who eat lots of sugar substitutes are different from those who do not. It could be, for example, that some consumers of these sweeteners are people who are already at high risk for diabetes or heart disease and looking to eat more healthily. Even without a smoking gun, however, the overall body of research was concerning enough to prompt the World Health Organisation to issue, in 2023, precautionary advice against the use of sugar substitutes as a means to control weight or prevent chronic diseases. (The advice does not apply to people with diabetes.)

There are plenty of hypotheses concerning how sugar substitutes could be causing harm. Some of these substances have been found to activate the same harmful gut and metabolic signalling mechanisms as sugar, and some studies in mice suggest that they could be affecting the function of immune cells involved in preventing the growth of tumours. Emerging evidence also suggests that they can affect the relative abundance of various gut bacteria, potentially tipping the scales in favour of harmful species. There are lots of open questions to be answered regarding the safety of sugar substitutes, says Herbert Tilg from the Medical University of Innsbruck, in Austria, but these studies are raising the level of concern.

Avoiding the most worrisome sweeteners is easier said than done. Food and drink manufacturers often use several in parallel (for example combining a substance that elicits instant sweetness with one that generates a lingering taste). This means that regular consumers of pre-packaged snacks or carbonated, energy and protein drinks will find them hard to avoid. The prudent thing to do is eschew these products altogether. And if you are hankering after something sweet, the best choice is a piece of your favourite fruit. ■