What we’re learning about the most popular sugar substitutes

• While no artificial sweeteners are currently labeled as carcinogenic, the World Health Organization (WHO) has identified aspartame (common in diet sodas and dozens of other processed foods) as possibly carcinogenic. 
• Many sweeteners on the market have not been thoroughly studied in humans, but the WHO has stated that their use does not aid in weight control, and may actually increase the risk of type 2 diabetes and heart disease. 
• Even at low doses non-sugar sweeteners (NSSs) have been shown to alter the gut microbiome, increase risk of glucose intolerance, increase inflammatory markers, and alter metabolic response.
• THE VERDICT: More and better studies are needed to determine the long-term health impacts of NSSs. Until they are better understood, the safest option is to limit your consumption.

The problem with sugar 

In the last several years, sugar has crystallized as a major health concern across a spectrum of diseases. A source of non-nutritive calories, sugar is a significant contributor to obesity and metabolic diseases such as type 2 diabetes, both of which are known risk factors for several cancers. Consuming too much sugar can lead to fatty liver disease (a precursor to liver cancer) and cause inflammation (which increases the risk for multiple forms of cancer). 

Compounding these negative health impacts is sugar’s highly addictive nature. Numerous studies have shown that sugar is as addictive (or even more addictive) than cocaine^[1]. While there’s no evidence that refined sugar is intrinsically dangerous in small doses, it has no health benefits, and the changes sugar can cause in cravings and appetite can have wide-ranging impacts on your health.

Common artificial sweeteners 

Non-sugar sweeteners (NSSs) promise to offer all the sweetness of sugar with little or low caloric impact. The following sweeteners have been approved by the FDA:

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The FDA has also approved additional plant-based sweeteners: luo han guo (monk fruit extract, sold as PureLo or Monk Fruit in the Raw) and thaumatin (from the katemfe fruit, sold as Talin). 

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Sugar alcohols are a third class of approved sweetener which are as sweet or slightly less sweet than sugar. Examples include xylitol, lactitol, sorbitol, mannitol, erythritol, and maltitol. 

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Rigorous long-term studies of these NSSs aren’t particularly robust, but there is emerging evidence that many have significant negative impacts on human health. 

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Aspartame: possible carcinogen

In 2023, the World Health Organization labeled aspartame a “possible carcinogen,” and indicated that further research into the issue is warranted. The designation was based on a review of studies^[2] linking aspartame consumption to increased incidence of liver cancer in humans^[3], as well as a study showing increased cancer risk in animals. 

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There has been significant debate about this designation, and the FDA has stated in no uncertain terms that it believes aspartame is safe when recommended daily limits are observed. That said, the American Beverage Association lobby has a significant interest in keeping aspartame and other NSSs labeled “safe,” and there is strong evidence that powerful lobby groups influence FDA decisions.^[4]

While the evidence on aspartame’s carcinogenicity might not be definitive yet, there is clearly very real cause for concern. 

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NSS impacts on gut microbiome 

The scientific community is only just beginning to understand the significance of the microbiome on human health, but the impact of dietary changes on the microbiome have been widely documented. The makeup of one’s microbiome has been convincingly tied to risk for diabetes, metabolic syndrome, and obesity. 

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A study focused on aspartame, sucralose, and saccharin showed all three compounds changed the composition of the microbiome even at low doses^[5]. These changes reduced glucose tolerance–lowered glucose tolerance is considered a precursor to type 2 diabetes. 

Additional studies showed that stevia extract and various sugar alcohols might also alter the gut microbiome, though the potential follow-on effects of these shifts is still unclear.^[6] 

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While these studies have not definitively linked NSS consumption to increased risk for cancer, the fact that these sweeteners impact the human microbiome at all is troubling; they are meant to be “metabolically inert,” passing through the digestive tract with no absorption or impact whatsoever. Moreover, type 2 diabetes and other metabolic disorders are known risks for multiple cancers. 

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NSSs and metabolic dysregulation

The promise of NSSs is that they are “healthier” alternatives to sugar–replacing sugar in beverages or foods with these low or no-calorie alternatives should theoretically eliminate the manifold health risks associated with excessive consumption of sugar.

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However, numerous studies have shown that NSSs not only don’t have the intended effect, they may in fact increase risk for obesity, type 2 diabetes, and cardiovascular events. While no direct links between NSSs and cancer have been confirmed, the impact of obesity and metabolic disorders on cancer risk is well-established.

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Emerging evidence suggests this might be because consuming NSSs interferes with the body’s signaling system; sweetness leads the body to anticipate the need to metabolize glucose (sugar) via insulin. When the body doesn’t encounter the glucose in the digestive tract that the sweet flavor led it to anticipate, it adjusts its response to the sweetness signal, weakening insulin sensitivity regardless of whether future sweet flavors are tied to glucose or an NSS.^[7] 

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What about allulose? 

Many new products use allulose, a sugar which occurs naturally in some foods such as figs, raisins, and molasses.^[8] About 70% as sweet as sugar, proponents note that it’s significantly lower in calories and isn’t absorbed by the body. 

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A relatively new substance, it has been allowed by the FDA but not approved, and studies of the compound are still rare. Early animal studies indicate it does alter the gut microbiome, and there’s some speculation that in human subjects these alterations could lead to adverse effects.

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Most NSSs have not been rigorously studied, which means that it’s impossible to definitively tie them to specific health outcomes. However, emerging evidence shows that their impact on the body is not nearly as neutral as has been promised. Even NSSs that show no direct links to cancer are implicated in overall changes to the body’s metabolic pathways, and a reduction in insulin sensitivity is a known precursor to type 2 diabetes. 

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As more and better studies are conducted, it’s possible that many, if not most artificial sweeteners will be shown to pose significant health risks. 

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Consumed in small amounts, NSSs are likely no more dangerous than consuming similar quantities of refined sugar. That said, until the effects on the body are better understood, the safest approach is to limit consumption of these products.

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