The Search for the Ideal Sugar Alternative: Sweeteners Explained

As behavioral scientists focused on appetite and obesity, designing trials with sweeteners appeared to be a straightforward endeavor. Our strategy was uncomplicated: substitute added sugar in various food items with diverse categories of alternative sweeteners while maintaining consistency in all other aspects.

Our initial test subject was a simple biscuit filled with fruit, and we planned to expand from there. In each instance, we aimed to analyze the impact on participants’ dietary preferences, metabolism, and overall health outcomes.

We presented this idea to our collaborator, Alain Le Bail, a seasoned professor and food scientist from France with over three decades of experience. His reaction suggested we had proposed something bizarre—like constructing a bridge made of marshmallows.

“Sugar,” he explained, “is not merely sweet. It contributes to a product’s structure, texture, browning, moisture, and mouthfeel. Eliminating it doesn’t just modify the biscuit; it undermines the very essence that defines it as a biscuit.”

If even we, as researchers in appetite and nutrition, find ourselves grappling with these intricacies, what can the average consumer expect?

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Sweeteners, a broad category comprising sugar substitutes and sweetness enhancers, were once relatively niche. Previously, they were primarily employed to lighten soft drinks or sweeten low-calorie yogurts; their use didn’t extend much further. Today, however, they can be found on nearly every supermarket shelf.

Sweeteners are central to ongoing global discussions regarding obesity, diabetes, child nutrition, and ultra-processed foods. Politicians considering sugar taxes, healthcare professionals assisting diabetic patients with dietary management, and parents struggling with product labels all encounter sweeteners as unavoidable elements.

They inspire a plethora of conflicting headlines. While we strive to balance our inherent desire for healthier choices with our collective discomfort around “artificial” additives, sweeteners are alternately portrayed as beneficial dietary allies or hazardous hormone disruptors. Rarely, however, are they regarded as ingredients with precise, measurable functions. The situation is further complicated by the surprising lack of robust scientific evidence in this area.

To grasp the capabilities and limitations of sweeteners, we must look beyond the oversimplified dichotomy of “good” versus “bad” and focus on more nuanced inquiries. What exactly are they substituting? In which contexts are they deployed? Who benefits from their use? And what intended outcomes are we aiming for?

Furthermore, what lies ahead for sweeteners? Will innovations such as artificial intelligence revolutionize their development? Are we any closer to achieving the ideal sugar substitute? As we contemplate the trajectory of sweeteners, it’s clear that this has been a long-standing quest.

A Brief History of Sweeteners

For over a century, sweeteners have promised the delightful taste of sugar without the accompanying calories or associated health risks—essentially offering guilt-free enjoyment. Yet, every breakthrough has faced backlash, contributing to a complex history marked by safety concerns and shifting public perceptions.

The modern narrative of sweeteners began in the late 19th century with the serendipitous discovery of saccharin at Johns Hopkins University in Baltimore, USA. This compound, derived from coal tar, boasts sweetness levels 300 to 500 times greater than those of sugar.

It quickly garnered acceptance among diabetic patients and, later, among calorie-conscious consumers. Critique arose over its taste, safety, and “unnatural” origins, yet its prevalence expanded—especially during sugar shortages experienced in the world wars.

In the years following, saccharin became prevalent in diet beverages and tabletop sweeteners, although safety concerns and the emergence of newer sweeteners diminished its popularity.

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In the early 20th century, other synthetic sweeteners like dulcin and P-4000 also appeared, but safety worries soon led to their withdrawal. Cyclamate, discovered in 1937, gained momentum in the post-war era, particularly in the United States.

Initially marketed as a diet aid and widely used in soft drinks, cyclamate faced a sudden ban in 1969 by the U.S. Food and Drug Administration (FDA), amid concerns regarding bladder cancer. Though the evidence was debated—research with rats suggested they consumed the equivalent of 550 cans of diet soft drinks daily—the ban on cyclamate was never lifted, leaving a lasting impact on public trust regarding sweeteners.

The next significant shift occurred when the FDA approved aspartame for use in soft drinks in 1983, ushering in what could be dubbed the “Diet Coke era.” It was later authorized as a general-purpose sweetener in 1996.

Compared to saccharin, consumers found aspartame’s taste to be more akin to that of sugar. An early comparative study showed that soft drinks sweetened with aspartame were statistically equivalent to those sweetened with sugar (sucrose) in various taste assessments, whereas drinks sweetened with saccharin had a noticeably bitter or metallic aftertaste.

Though aspartame does have a slightly different taste profile than sugar, it quickly became the go-to option for those conscious of their weight as well as in the food industry, particularly in the U.S. and U.K. Negative perceptions regarding aspartame, however, have persisted. A 2021 study from Canada revealed that 52% of respondents considered aspartame less healthy than table sugar, favorably comparing other sweeteners perceived as more “natural.”

Aspartame has issues linked to its chemical composition; it contains the amino acid phenylalanine, harmful to individuals with the rare disorder phenylketonuria. Consequently, products with aspartame often carry warning labels about this risk in several regions, including the U.S. and U.K.

Media reports have also amplified speculative risks surrounding aspartame, such as claims of brain cancer, despite a lack of robust evidence. Regulatory bodies such as the FDA and the European Food Safety Authority (EFSA) still deem aspartame safe in the amounts currently approved for use.

Yet skepticism from consumers remains—a phenomenon with commercial repercussions. In 2015, PepsiCo reformulated Diet Pepsi in the U.S. to exclude aspartame, yet due to poor performance, the ingredient was reintroduced after the reformulated product did not meet sales expectations.

Subsequent sweeteners focused on improved sensory profiles and functionalities. Acesulfame-K (ace-K) and sucralose emerged in the 1990s and 2000s, as they generally performed better under heat and had longer shelf lives. For example, aspartame is unsuitable for baking or sauce-making due to its breakdown under high temperatures and diminishes in sweetness over time in long-shelf-life products like certain condiments and dried mixes.

However, ace-K and sucralose typically work better in combinations. For instance, ace-K enhances initial sweetness but leaves a bitter aftertaste that other sweeteners can help balance out.

The acceptance of “artificial” sweeteners varies by region. They appear to be more embraced in the U.K. and Germany, while receiving less favorable reception in countries like Portugal and Romania. Factors influencing this variability include regulatory approval, cultural preferences, and attitudes toward health.

The 2010s saw a marked preference for natural sweeteners with botanical origins. Stevia, extracted from the leaves of the Latin American plant Stevia rebaundiana, was the first to gain significant traction, followed by monk fruit, sourced from the Siraitia grosvenorii vine in southern China.

Nevertheless, these natural sweeteners come with trade-offs. For instance, stevia’s flavor can present unpleasant bitter or licorice notes. Additionally, various natural sweeteners pose challenges when sugar’s structural properties become critical, such as in terms of mouthfeel, browning, and moisture retention.

This requirement for bulk has led to the rise of polyols as important alternatives. Often referred to as sugar alcohols, polyols encompass erythritol, isomalt, maltitol, and sorbitol. They are typically synthesized industrially using corn and wheat syrups.

Polyols can be incorporated into products in larger quantities since they are less sweet than sweeteners like aspartame and stevia. They help replicate sugar’s volume and texture, allowing for a decrease in caloric content and a reduced risk of tooth decay.

However, excessive consumption of polyols can lead to gastrointestinal discomfort, inducing laxative effects. For this reason, in the U.K. and EU, for instance, food products with over 10% polyol content must clearly label a laxative warning.

In total, around 20 different sweeteners are approved for use in the U.K. However, each sweetener has its own advantages and disadvantages, leading to the absence of a one-size-fits-all sugar replacement.

Instead, food manufacturers employ a mix-and-match strategy, blending various ingredients to mimic the sweetness and structure that sugar provides. The resulting products generate substantial annual sales globally, but innovations must contend with a public whose opinions on sweeteners are continually evolving. Indeed, this same cycle has reemerged in the 2020s.

How Sweeteners Became Controversial (Again)

To comprehend the recurring controversies surrounding sweeteners, it’s essential to understand how scientific evidence translates into public health guidelines and governmental policies. The World Health Organization (WHO) sets international standards and offers evidence-based policy options in this realm, typically targeting free sugars—any sugars added to products and those present in everything from honey to fruit juice concentrates.

The WHO has consistently advised that adults and children limit free sugars to less than 10% of total caloric intake to mitigate risks of tooth decay and excessive body weight, suggesting an even stricter limit of below 5% for long-term dental health.

Most guidance regarding sweeteners has derived from food safety authorities, focusing primarily on safety and exposure as opposed to potential health advantages. In the U.K., where guidelines have been relatively positive, the government initiated a sugar reduction programme in 2016, preceding a broader obesity strategy directed by both the WHO and the U.K. Scientific Advisory Committee on Nutrition.

The sugar programme actively encouraged industry and consumers alike to replace sugar with sweeteners, which included the implementation of a soft drinks industry levy (“sugar tax”) in 2018, aimed at manufacturers producing drinks with excessive sugar content.

While this led to a notable increase in sweetener quantities found in consumer products, the landscape shifted unexpectedly in 2023. The WHO unexpectedly intervened in the sweetener discourse by recommending against the use of sweeteners as a strategy for weight management or disease risk reduction.

This recommendation was informed by a 2022 systematic review—a comprehensive survey of various studies—conducted by the WHO. The review indicated that while rigorous short-term studies (up to one year) showed minor weight-loss benefits from replacing sugar with sweeteners, long-term observational studies suggested heightened risks of obesity, type 2 diabetes, and cardiovascular diseases.

Observational studies track how individuals consume sweeteners voluntarily and assess their health outcomes. As we will explore further, several limitations in these studies make the findings less reliable.

The strongest methodology for determining causes behind specific health conditions involves randomized controlled trials. In this context, such trials assign participants to receive foods made with different types of sweeteners to compare their outcomes.

We’ll delve into these specifics shortly. However, when sweeteners replace sugars in these studies, researchers typically observe modest reductions in body weight and caloric intake. In randomized trials contrasting sweeteners with water, nothing, or placebos, no negative effects on participants’ body weight or energy intake were noted, nor were there any reported adverse effects.

The WHO’s recommendation reflects this uncertainty regarding the balance of benefits versus harms, suggesting that countries may still encourage the use of sweeteners if evidence clearly supports their safety and efficacy. This conditionality is typical for the WHO when there’s uncertainty about the evidence base.

In the U.K., this uncertainty has arguably raised perceptions of sweeteners as “controversial.”

In 2025, the Scientific Advisory Committee on Nutrition released a comprehensive response stating that the WHO had placed more emphasis on observational studies than randomized controlled trials. It also acknowledged the mixed quality of evidence supporting the recommendation. However, it further advised minimizing sweetener intake overall and stated that young children should avoid beverages sweetened with both sugar and sweeteners.

At the international level, several instances have arisen where policy development has outpaced evidence. Products involving sweeteners fall under the category of “ultra-processed foods” according to NOVA classification criteria, a contentious system created by Brazilian researchers approximately 15 years ago. The NOVA definitions are considered value-laden, ambiguous, and lacking clarity regarding distinctions between processing, formulation, and nutritional quality.

This NOVA classification has contributed to significant shifts in U.S. sweetener policies. New U.S. dietary guidelines now assert that no amount of added sugars or sweeteners should be perceived as part of a healthy or nutritious diet.

Broadly, the international narrative has shifted from “substituting sugar with sweeteners” to “reducing overall sweetness in the diet.” While theoretically promising, this notion is poorly evidenced and politically challenging to implement.

Why Sweetener Research Can Be Confusing

The science surrounding sweeteners and health generally falls into three categories:

1. Mechanistic experiments to illustrate how sweeteners impact biological processes;
2. Observational studies correlating sweetener consumption with certain outcomes;
3. Randomized controlled trials assessing the actual health effects of sweeteners in controlled environments.

Mechanistically, sweeteners induce measurable biological changes in the body. They activate taste receptors, affect blood sugar levels following consumption, influence hormone secretion, alter brain response to sweetness, switch on or off specific genes, and modify the abundance of certain gut microbes.

These mechanistic findings confirm that sweeteners have tangible effects within the body. However, they do not serve as conclusive proof of harmful or beneficial outcomes. An alteration in hormones, brain activity, or gut microbiota does not inherently mean individuals will consume more or experience weight gain or increased disease risk. Mechanistic findings should thus be seen as indicators that warrant further examination in everyday contexts.

The gut microbiome serves as a prominent illustration of this gap. While sweeteners may influence gut microbial profiles and subsequently impact metabolism, findings can be highly variable based on the sweetener consumed, the quantity ingested, the individual, and the broader dietary context. Consequently, a microbiome finding may be scientifically intriguing without providing clarity on whether sweeteners, consumed in regular diets, yield net positive or negative effects.

Observational studies involve following large cohorts over time, linking reported sweetener consumption with outcomes like weight gain, diabetes, cardiovascular diseases, and mortality rates. Such studies are indispensable for exploring questions that randomized trials typically struggle to address, particularly regarding rare conditions and diseases that develop over extended periods. They are also vital for tracking consumption patterns and generating hypotheses. However, these studies are particularly susceptible to misinterpretation.

One challenge is measurement accuracy. Researchers usually estimate individuals’ sweetener intake based on self-reported dietary questionnaires which categorize foods broadly, such as “diet soft drinks.”

These seldom capture the type or amount of sweeteners consumed, especially since manufacturers frequently alter their ingredients. Consequently, researchers risk misclassifying data when linking specific sweeteners to health outcomes.

A prominent issue is known as reverse causality. Research shows that sweeteners are disproportionately utilized by individuals already striving to manage their weight, control blood sugar, or enhance their diets. This tendency often arises because these individuals are beginning with higher or rising risks of diet-related health concerns.

In such cases, sweetener consumption likely signals existing health vulnerabilities or behavioral changes rather than being a causative factor for later health issues. Researchers can adjust statistical analyses to account for these individuals, but it’s challenging to fully disentangle motivations and lifestyle factors.

Lastly, sweeteners exist within what is termed an additive versus substitutive problem. Comparative research rarely pits sweeteners against a complete absence of sugar (additive); instead, the focus is usually on sweeteners as replacements for sugar (substitutive). Comparisons of unique types or blends of sweeteners are even more infrequent.

Changing the parameters can yield different conclusions, yet discussions surrounding sweetener safety often conflate findings from disparate studies. It’s only when these complexities are acknowledged that the most robust human evidence becomes clearer to interpret.

It’s crucial to stress that not all misinterpretation falls squarely on policymakers. The design, analysis, and communication of studies can also render the evidence appear contradictory. The risk of misunderstanding heightens when tentative mechanistic signals are treated as definitive proof of everyday harm or when observational links are equated with randomized trials.

What the Best Human Evidence Shows

The crux of the matter regarding sweeteners lies in understanding what occurs when they replace sugar, rather than when they are consumed alongside an otherwise unaltered diet. This distinction is vital because we would expect lower calorie intake and diminished spikes in post-meal blood sugar and insulin levels if someone consumes less sugar.

This leads to two key scientific questions: First, do sweeteners alter eating behaviors by increasing food intake or modifying food preferences? Second, do any short-term changes yield significant long-term implications for body weight and health?

One of the most compelling bodies of evidence emerges from a series of recent randomized controlled trials conducted in realistic dietary conditions. Each trial involved collaborative teams from various institutions and sometimes different countries, often referred to by abbreviated titles: Sweet Tooth, Switch, and Sweet.

For instance, in a trial within the Sweet project, adults experiencing overweight or obesity consumed various beverages sweetened with one of three discrete blends, with a fourth alternative sweetened solely by sugar. Two of the three blends utilized plant-based combinations including stevia—one paired with monk fruit and another with katemfe fruit (known as thaumatin). The third option combined sucralose and ace-K. All participants received one of these drinks followed by a carbohydrate-rich breakfast.

Executed by multiple teams from different universities, these were crossover trials, whereby participants consumed each drink at different times. All three sweetener blends resulted in reduced insulin production post-meal when contrasted with the sugar-sweetened drink. Additionally, the blends consisting of sucralose/ace-K and stevia/katemfe fruit observed lower blood sugar increases.

Although minor variations were noted among blends regarding appetite effects, these did not translate to higher caloric intake during the subsequent 24 hours. In simpler terms, the advantageous outcomes on blood sugar and insulin levels didn’t lead participants to overcompensate through increased eating. Gastrointestinal reactions were predominantly mild.

Switching sugar for sweeteners in solid foods poses greater challenges due to sugar’s additional structural benefits. We had to address these complexities to assess the effects of sweeteners in biscuits in our study, referenced earlier in this article, which was part of the Sweet project.

In that study, we created biscuits with fruit fillings using three approaches: sugar, stevia, or a neotame variant resembling aspartame. We analyzed participants between servings and after two weeks of daily consumption. This methodology also employed a crossover design.

Participants consuming biscuits made with sweeteners again exhibited lower spikes in both blood sugar and insulin after meals—both after one serving and following the two-week trial. Their levels of hunger and appetite hormones did not demonstrate significant differences. This represents one of the more rigorous tests addressing the assertion that sweeteners in solid foods may increase hunger or disrupt appetite-regulating hormones, prompting increased eating.

These findings are reassuring, yet the critical policy question ultimately concerns longer-term impacts. The Sweet project has addressed this through a 12-month randomized controlled trial involving adults with overweight or obesity. This trial engaged multiple research teams and aimed to replicate typical sweetener usage in everyday scenarios.

Participants first underwent a two-month low-calorie diet designed to lose at least 5% of their body weight (the average loss was around 10 kg or 22 lbs). Following this period, they transitioned to a healthy diet wherein no more than 10% of their caloric intake could derive from sugars.

One group adhered to the 10% criterion by replacing sugar-rich products with those containing sweeteners, while the other group achieved the standard by avoiding both sugars and sweeteners entirely.

At the end of the year, both groups maintained most of the weight they initially lost. However, participants using sweeteners had regained less—approximately 1.6 kg on average—compared to the other group, which regained about 3.5 kg. This indicates that incorporating sweeteners into a healthier, low-sugar diet may assist individuals in retaining their weight loss.

The trial did indeed reveal variations in the gut microbiomes of the two groups, with the sweetener-using participants showing a greater prevalence of microbes associated with short-chain fatty acid and methane production. These microbes can lead to bloating or constipation, but there was no evidence indicating that sweetener consumption worsened measures related to risks for diabetes or heart disease (known as cardiometabolic markers).

What could clarify the difference in weight management outcomes for the sweetener group? One possible explanation is that participants who avoided both sugar and sweeteners found their diet less manageable. The absence of sugar and sweet-tasting foods may have rendered the notion of a low-calorie diet more appealing, complicating efforts to sustain a lower-calorie eating pattern over time.

This interpretation was reinforced by the psychological data gathered during the study, which indicated lower satisfaction with diets and increased cravings for sweet flavors in the no-sweetener group, whereas the sweetener group did not experience similar shifts.

Evidence from weight management initiatives supports this perspective. A year-long randomized trial from the Switch project at the University of Liverpool compared beverages with sweeteners to consuming only water within a structured program aimed at promoting healthier eating, activity, and lifestyle changes for weight loss and maintenance. Both groups experienced weight loss and sustained meaningful reductions.

Participants using drinks with sweeteners lost slightly more weight than the water group, albeit the difference was marginal. The key takeaway is that diet soft drinks do not correlate with poorer weight control compared to plain water in a managed program. These outcomes challenge widespread beliefs that such beverages revive cravings for sweetness and trigger weight gain.

Ultimately, the Sweet Tooth project also conducted a randomized trial that addresses another frequent narrative: the idea that exposure to sweet flavors increases individuals’ preference for sweetness and encourages overeating.

During this six-month study, participants received low, moderate, or high levels of sweet-tasting foods and drinks, sourced from sugars, sweeteners, fruits, and dairy products.

By the study’s conclusion, the groups did not differ in their preference for sweetness or their selection of sweet foods. Additionally, there were no discernible effects on caloric intake, body weight, or cardiometabolic markers. In the subsequent months, participants returned to their pre-study preferences for sweetness.

This weakens the notion that simply “training the palate” through the elimination of sweet tastes is a reliable strategy for lowering caloric intake or enhancing weight regulation over the long haul.

These trials provide some of the strongest human evidence available and illustrate that the science around sweeteners is more coherent than the public discourse might suggest. In controlled settings, replacing sugar with approved sweeteners tends to lower post-meal spikes in blood sugar and insulin levels, does not elevate appetite, and can support weight management within the context of a healthier, reduced-sugar diet.

While these effects are not monumental, and sweeteners are not a singular solution to obesity, overall dietary patterns, food choices, and caloric density remain pivotal. Importantly, high-quality human trials do not uphold the notion that sweeteners, when used as alternatives for sugar, foster weight gain or cause metabolic harm.

One aspect readers may question is aspartame, which has been designated as “potentially carcinogenic to humans” by the International Agency for Research on Cancer. Nevertheless, this classification is based on limited evidence, primarily concerning liver cancer, and denotes a hazard potential rather than confirming that normal consumption has been shown to cause cancer in real-world situations.

The Joint FAO/WHO Expert Committee on Food Additives concluded that current human evidence does not substantiate claims of harm and retained the established acceptable daily intake levels. The FDA emphasized that this classification does not indicate a confirmed link between aspartame and cancer at present consumption levels.

The Future

Looking ahead, the focus should be on deepening our understanding. How do individuals utilizing sweeteners over many years sustain lower sugar intake, or do they merely shift preferences and purchasing patterns? Moreover, when studies detect changes in gut microbiota, do these hold significant implications for metabolic health?

We still need robust evidence involving populations of interest for policy-makers: children, individuals with diabetes, and those at the highest risk for cardiovascular problems and diabetes. This isn’t solely due to concerns about identifiable harm but also to ensure public health guidance is informed by real-world data.

Moreover, the science must offer answers to practical consumer-oriented questions. Key among these is a lack of understanding regarding which sweeteners, or combinations thereof, work best in specific products; how much sugar can be eliminated without compromising food and beverage acceptability; and whether these answers differ among children, adults, individuals with diabetes, or those who frequently consume sweeteners.

Another area of exploration involves getting closer to sugar itself. Sweet proteins such as brazzein and monellin, first identified in tropical fruits, are capturing interest as they provide substantial sweetness in minuscule amounts. The FDA has recently issued “no questions” letters approving them as food ingredients, allowing them to be used legally in commercial products.

Rare sugars such as tagatose and allulose also present promising possibilities. They may not be as sweet, but they mimic sugar’s taste and functionality more closely.

However, this does not imply we have found the perfect substitute. Sweet proteins can impart sweetness but do not provide the bulk, moisture retention, or browning that sugar does. Rare sugars may have characteristics more akin to sugar, but their behavior is product-specific, and production poses challenges—they are not naturally prevalent and must be synthesized through intricate processes. All these advancements should be viewed as promising steps, not as a definitive one-size-fits-all replacement.

Artificial intelligence may further aid this quest, albeit with no miraculous outcomes. Researchers are now employing machine-learning tools to predict sweetness and properties like bitterness and safety before candidate molecules are even evaluated within food products.

This has the potential to expedite the search for superior sweeteners and, perhaps more crucially, optimal blends for specific products. The future may hinge less on individual miracle ingredients and more on smarter combinations: sweet proteins for intensity, rare sugars for volume and mouthfeel, and refined formulations to better emulate the real deal.

While the prospect of having our cake and eating it is unlikely in the literal sense—given that sugar encompasses both sweetness and structure, with no single ingredient capable of replicating both—the growing body of evidence suggests that we can continue enjoying sweetness while lowering sugar consumption. In other words, although we may not have the same cake, we can appreciate alternatives that are less taxing on our bodies.

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