How does sucralose affect the body

Artificial sweeteners seem like a perfect way to satisfy a sweet tooth without the calories. Learn more about vaccine availability. Advertising Policy. You have successfully subscribed to our newsletter. Related Articles. Trending Topics. What Parents Need to Know. Is Sucralose Splenda Bad for You? Share this article via email with one or more people using the form below. A more recent study published in Cell Metabolism found that the consumption of sucralose in the presence of a carbohydrate rapidly impaired glucose metabolism and resulted in the dysregulation of gut-brain control of glucose metabolism.

Several years ago, researcher Xin Qin, M. Qin made this discovery when examining the rapid increase of IBS among Alberta, Canada residents over a period. In short, it went up percent. Sucralose has a more detrimental effect on gut bacteria than other artificial sweeteners, such as saccharin, because 65 percent to 95 percent of sucralose is excreted through feces unchanged.

In , Canada became the first country in the world to approve the use of sucralose as an artificial sweetener. In other words, there was a direct correlation between the amount of sucralose consumed and the increase in inflammatory bowel disease.

To answer some common questions concerning the safety of sucralose and digestion — does sucralose cause bloating? Does sucralose make you poop? Again, it can increase inflammation and cause IBS symptoms in some cases. Does sucralose affect gut bacteria? Essentially, the understanding we now have is that because the body cannot digest sucralose, it travels through the human gastrointestinal track and damages it as it goes.

It harms the intestinal wall, potentially causing leaky gut. Several studies have confirmed the harmful effects of sucralose on gut health. For instance, the Journal of Toxicology and Environmental Health published an animal study out of Duke University Medical Center describing that Splenda not only significantly reduces beneficial bacteria in the gut, but it also increases your fecal pH. That decreases the amount of nutrients you can absorb. A study published in the Journal of Toxicology and Environmental Health found that cooking at high temperatures with sucralose can generate dangerous chloropropanols, a potentially toxic class of compounds.

Although sucralose is commonly used in baked goods, studies show that the stability of the artificial sweetener decreases as the temperature and pH increase.

More research is needed for concrete evidence about the carcinogenic effects of sucralose. Thought using sucralose in your coffee was going to help you lose weight?

Well, it turns out that epidemiological studies in humans and lab studies in animals both suggest an association between using artificial sweeteners and body weight gain.

Plus, artificial sweetener use can increase the risk for metabolic syndrome, type 2 diabetes, hypertension and cardiovascular disease. In an month trial published in the New England Journal of Medicine , children completed the study were randomly assigned to receive an eight-ounce can per day of either a no-calorie sweetened or sugar-sweetened beverage that contained calories.

If you are uncertain about the health effects of sucralose it is best just to avoid this product. As an alternative to consuming sucralose limit the amount of added sugar in your diet to less than calories or 25 grams for most women and calories or 36 grams for most men.

Grand View Research. Accessed 25 July Splenda Sweeteners. The Calorie Control Counsil. The U. Accessed 28 July American Heart Association. Accessibility Information. Skip to main content.

Resources Our Products. In particular the consumption of sugar-sweetened beverages has been associated with cardiometabolic complications, driven by an increased energy intake and obesity Therefore, one common approach to improve energy balance is to refrain from sugars by replacing them with artificial sweeteners.

As artificial sweeteners offer a sweeter taste without calories, the replacement of sugars with these sweeteners seems promising in reducing sugar and energy intake. Meta-analyses of Randomized Controlled Trials RCTs have shown that daily energy intake after 4 or 10 weeks and sugar intake after 4 weeks were lower in healthy, overweight, and obese individuals receiving artificial sweeteners as a replacements of sugars in the diet Sweeteners are classified as natural sweeteners and artificial sweeteners.

Artificial sweeteners are further classified as nutritive and non-nutritive sweeteners, depending on whether they contain calories. The nutritive sweeteners include the monosaccharide polyols e. The non-nutritive sweeteners, known as artificial sweeteners, include substances from different chemical classes that are 30—13, times sweeter than sucrose Artificial sweeteners are metabolized differently and have different properties, including sweetness intensity, persistence of sweet taste, coating of the teeth, and aftertaste effects Therefore, each sweetener is unique and may affect the perceived taste or use in food applications differently Sweetener consumption is highly prevalent in both adults and children and is expected to increase even more in the near future.

Between these decades, a rise in food products containing artificial sweeteners occurred with more than 6, new products launched in the United states alone Currently, six different artificial sweeteners are approved by the Food and Drug Administration FDA as food additives in the United States, including saccharin, sucralose, aspartame, advantame, acesulfame-potassium, and neotame In the European Union, the range of approved artificial sweeteners is broader, as cyclamate, aspartame-acesulfame salt, and neohesperidin dihydrochalcone are also approved by the EU Scientific Committee on Food 22 — Other artificial sweeteners have not been assessed yet or are declared as unsafe for usage.

Despite the fact that many national authorities have recognized artificial sweeteners as safe and well-tolerated, a lot of controversies about the effects of sweeteners on human health still exist. Whereas, some longitudinal cohort studies show an association between artificial sweeteners consumption and reduced risk of T2DM, overweight and obesity, other observational studies have yielded opposite findings 25 — Furthermore, longitudinal cohort studies found a positive association between the consumption of artificial sweeteners and the risk of hypertension, stroke, and cardiovascular events Thus, although the use of artificial sweeteners seem promising in assisting weight loss, artificial sweeteners have been linked to a variety of health concerns, including obesity and its related cardiometabolic disturbances 29 — Importantly, however, it cannot be excluded that the associations found in these observational and prospective cohort studies studies are largely explained by an increase in artificial sweetener intake to compensate for an unhealthy diet or lifestyle in general reverse causation.

The safety and health benefits of artificial sweeteners consumption remain controversial. Therefore, the physiological health effects of artificial sweeteners should be elucidated. In this review, we provide an overview of the physiological effects of artificial sweeteners on body weight control and glucose homeostasis. Furthermore, the pharmacokinetics of the commonly used artificial sweeteners will be addressed to identify the controversies of the existing evidence surrounding their use.

Subsequently, effects of artificial sweeteners on body weight and glycemic control will be discussed. Ample data is available on the effects of artificial sweeteners on body weight and glucose homeostasis. Nevertheless, fewer studies are available reporting the effects of specific artificial sweeteners.

A review of the literature was conducted using PubMed databases in the period January—April Articles written in English language were included. No data restrictions were applied. Reference lists of relevant systematic reviews were screened to identify further relevant citations. Human studies were mainly selected for this review to address the effect of artificial sweeteners on parameters related to body weight or adiposity and glucose homeostasis.

In case of limited or lacking human data, rodent studies and in vitro studies were also considered. Studies in healthy adults as well as adults living with overweight, obesity or diabetes were included. RCTs including weight-loss studies , prospective cohort studies, cross-sectional studies, and meta-analyses were included in the literature search. Studies included the use of artificial sweeteners solely, without carbohydrate or caloric content modification, unless specified otherwise.

Furthermore, studies that did not specify the type of artificial sweetener were excluded. We have identified 5 meta-analyses of RCTs or RCTs studying the effects of specific artificial sweeteners on adiposity and 20 meta-analyses of RCTs or RCTs studying the effects of specific artificial sweeteners on glucose homeostasis as indicated in Tables 1 , 2 , respectively.

Retrieved papers were first screened by title and subsequently by abstract based on the criteria. Full papers were reviewed in case the abstract was insufficient to determine the eligibility. Endnote X8 was used for the management of articles and citations. In total, publications were identified that matched these criteria.

Table 1. Characteristics of human studies investigating the effect of specific artificial sweeteners on body weight or adiposity. Table 2. Characteristics of human studies investigating the effect of specific artificial sweeteners on glucose homeostasis. To determine safety of artificial sweeteners the FDA considers probable intake, cumulative effects from all uses, and toxicological data in animals.

The European Food Safety Authority EFSA evaluates and confirms that the intake of artificial sweeteners, within the acceptable daily intake ADI , does not cause cancer or other health-related problems, and are therefore safe for human consumption 56 , Although authorities consider artificial sweeteners as safe as they do not pose any health-related problems, when consumed within the ADI, no specific safety claims have been made about the effects of sweeteners on non-communicable diseases, such as obesity and T2DM.

Despite the fact that several artificial sweeteners are tested for pharmacological and toxicological aspects, the concerns about the effects of unmetabolized compounds on non-communicable diseases still exist. Artificial sweeteners have distinct structures and are metabolized differently as some but not all are digested or fermented Figure 1. The most common artificial sweeteners such as acesulfame potassium, saccharin, aspartame, sucralose, and steviol glycoside will be discussed in the present review.

Figure 1. Overview of the major routes of absorption, digestion, metabolism, and excretion of different types of artificial sweeteners. A Acesulfame-K, saccharin, and sucralose.

Acesulfame-K is completely absorbed into the systemic circulation to be excreted in the urine via the kidneys. The majority of saccharin is absorbed and distributed, while the remaining amount passes the gastrointestinal tract to be eliminated in the feces.

Most of the sucralose passes the gastrointestinal tract to be eliminated in the feces, while a small amount is directed toward the kidneys to be excreted in the urine. B Aspartame and steviol glycoside. Aspartame is digested in the small intestine and the hydrolyzed components are absorbed and metabolized following their normal metabolic pathways. Steviol glycoside is fermented by the gut microbiota to form steviol, which is absorbed into the liver and excreted in the urine.

Acesulfame-K, acesulfame potassium. Due to the higher intensity and the longer persistence of the sweetness, acesulfame-K is used in a wide range of products, mainly soft drinks. Although this sweetener contains potassium, its intake does not influence systemic potassium levels Acesulfame-K is not metabolized by the body Following ingestion, acesulfame-K is completely absorbed into the systemic circulation and distributed 58 , 62 Figure 1.

The absorption of acesulfame-K is very rapid, thereby making it unlikely that it will reach the lower gastrointestinal GI tract to impact the gut microbiota upon administration of a normal ADI-dosage Saccharin 1,1-dioxo-1,2-benzothiazolone is available in three different forms: in acid form, or bound to sodium or calcium The most common form is sodium salt due to its high solubility and stability.

Similarly to acesulfame-K, saccharin is not metabolized by the body Therefore, the FDA considers saccharin as safe Therefore, a fraction of saccharin that is not immediately absorbed is able to affect the gut microbiota composition Aspartame 3S amino[[ 2S methoxyoxophenylpropanyl]amino]oxobutanoic acid is approximately times sweeter than sucrose In contrast to other artificial sweeteners, aspartame contains 4 calories per gram.

Nevertheless, due to the sweetening intensity, only a small amount of aspartame is used in products to achieve sweetness. Therefore, few calories are derived from aspartame in sweetener products.

Upon ingestion, aspartame is broken down in the small intestine by esterases and peptidases to aspartic acid, phenylalanine, and methanol 16 , 67 Figure 1. Only the hydrolyzed components are absorbed into the circulation and metabolized following their normal metabolic pathways Methanol is metabolized in the liver, while aspartate acid and phenylalanine enter the free amino acid pool.

Thereupon, the components are taken up by peripheral tissues, utilized for protein synthesis and metabolism, and excreted. Aspartame does not accumulate in the body as it is rapidly digested Neither aspartame nor its components reach the colon. Therefore, aspartame is not able to affect the gut microbiota 58 , Sucralose 2R,3R,4R,5R,6R [ 2R,3S,4S,5S -2,5-bis chloromethyl -3,4-dihydroxyoxolanyl]oxychloro hydroxymethyl oxane-3,4-diol is very similar to sucrose in structure.

However, the three hydroxyl groups attached to the sucrose molecule are replaced by chlorine atoms, thereby changing the confirmation of the molecule, to form sucralose Thus, glycosidic enzymes are unable to recognize and digest sucralose.

Although sucralose is made from sugar, it provides no calories as it is not digested in the body 16 , Sucralose is times sweeter compared to sucrose. Nevertheless, sucralose was found to be non-nutritive to bacteria and resistant to fermentation, while affecting microbiota through bacteriostatic effects Steviol glycosides Hydroxykaurenoic acid are the chemical compounds responsible for the sweet taste and can be found on the leaves of the South American plant Stevia rebaudiana Steviol glycosides cannot be hydrolyzed by the digestive enzymes and acids present in the upper GI tract 58 , Nevertheless, the microbiota in the colon, primarily Bacteroides, is able to degrade steviol glycosides Therefore, steviol glycosides are able to modulate the gut microbiota as they encounter it directly.

Steviol glycoside is degraded by cleavage of the glycoside linkage, thereby forming steviol, steviolbioside, and glucose 76 — 78 Figure 1. In turn, steviolbioside will be converted to steviol The formed glucose is either utilized by colonic bacteria or absorbed, metabolized, and excreted into the expired air as carbon dioxide and water, while steviol is absorbed and enters the liver via the portal vein 79 , Nonetheless, the entry of steviol into the portal vein is slow due to the slow metabolization by the colonic bacteria, depending on the species In the liver, steviol is glucoronidated and excreted into the urine 82 , An increased body weight and adiposity develop under conditions of a positive energy balance.

The regulation of energy balance is a complex process that involves homeostatic regulation of energy intake and energy expenditure. Although artificial sweeteners are as sweet or even sweeter than natural sugars, the caloric content and the metabolism routes are different. Therefore, it is likely that artificial sweeteners may affect energy balance, and thus body weight, differently compared to natural sugars via underlying physiological processes comprising the gut microbiota, the reward-system, and adipogenesis Figure 2.

Considering the increase in the prevalence of overweight and obesity and the rising interest in losing weight, preventing weight gain and maintaining weight loss, it is important to elucidate the effects of artificial sweeteners on body weight control.

Furthermore, Azad et al. Interestingly, however, other meta-analysis of RCTs 4 weeks to 40 months showed that the intake of artificial sweeteners resulted in reduced body weight in overweight and lean individuals compared to sugar or water Notably, however, this meta-analysis included 4 out of 12 intervention studies carried out in the context of a weight loss program Nevertheless, these findings strongly suggest that artificial sweeteners may have neutral or beneficial effects on long-term body weight control.

Figure 2. Overview of the mechanisms of how artificial sweeteners may affect physiological processes involved in body weight regulation. Artificial sweeteners interact with T1R-family of sweet-taste receptors in the oral cavity and gastrointestinal tract, thereby able to affect satiety and, in turn, energy intake and body weight. However, in vivo studies have shown no effect of artificial sweeteners on the secretion of incretins.

Furthermore, several artificial sweeteners may reach the adipose tissue to interact with T1R-family of sweet-taste receptors and affect adipogenesis and, in turn, body weight. Moreover, several artificial sweeteners are able to induce gut microbiota alterations.

Thereupon, SCFA production is enhanced. It can be speculated that SCFA may, in turn, increase energy expenditure due to enhanced lipid oxidation and affect satiety by modulating gut-brain signaling via incretins. Considering specific types of artificial sweeteners, meta-analyses, based on RCTs, showed no effect of aspartame consumption on body weight compared to sugar or water in individuals with either obesity or T2DM 34 Table 1.

Only studies wherein aspartame was evaluated alone were included in the meta-analyses to clarify the specific effects of aspartame without interference of results obtained due to the consumption of other sweeteners. However, large heterogeneity was found due to different treatment patterns for aspartame and sugar or water. Similarly, meta-analysis, based on RCTs, showed no effect of steviol glycoside consumption on BMI compared to talcum, maize starch, or unspecified matching placebo in healthy individuals and patients with diabetes Additionally, subgroup analyses showed no significant effect of steviol glycoside on BMI in either healthy individuals and patients with diabetes.

The results indicate that these artificial sweeteners do not affect body weight. However, the effects of acesulfame-K and saccharin can still be debated, as there is no consistent evidence, and meta-analyses are lacking. Furthermore, saccharin consumption was found to increase body weight in mice compared to water, sucrose or glucose, whereas other studies in rodents have shown reduced or unchanged body weight compared to mice receiving water, glucose, fructose or sucrose 87 — However, the absorption of saccharin is lower in rodents compared to humans due to a relative higher stomach pH in rodents Furthermore, differences in perception of sweetness for individual artificial sweeteners exist between different rodent species and strains Therefore, perception and post-ingestive responses of rodents might differ from humans.

Nevertheless, human data on the effect of acesulfame-K on body weight is currently lacking. Moreover, human data on the effect of saccharin on body weight is scarce with only one study showing no significant effects on body weight after 12 weeks of saccharin consumption compared to sucrose in overweight and obese individuals Moreover, sucralose consumption has been reported to have no effect on body weight in mice compared to water, and in human studies compared to placebo calcium carbonate or control no-intervention 37 , 38 , 85 , 88 , Notably, contradictory results from rodent studies for the effect on body weight exist only for acesulfame-K and saccharin, which are largely or entirely absorbed in their intact form, thereby being able to reach the peripheral tissues.

Consistently, rodent and human studies found no effect of sucralose on body weight as only a small amount is absorbed in its intact form, thereby reaching the microbiota in a larger amount compared to acesulfame-K and saccharin 37 , 38 , 85 , 88 , As artificial sweeteners have different metabolic fates, differences in physiological effects affecting energy balance and adiposity should be elucidated.

As artificial sweeteners contain no or low amounts of calories, one might expect that these sweeteners may contribute to lower energy intake and thus body weight reduction.

Nevertheless, controversies exist whether artificial sweeteners affect appetite, hunger, and eating behavior, and if these effects are beneficial or not. One driving aspect in eating behavior is the reward of food. The reward system plays an important role in regulating energy intake, and can be divided into sensory and post-ingestive reward 19 , After ingestion of either natural sugars or artificial sweeteners, gustatory information is perceived by sweet taste receptors, which are heterotrimeric G-protein coupled receptors GPR consisting of two subunits, namely taste receptor type 1 member 2 T1R2 and 3 T1R3 98 , The binding sites of sweet taste receptors are different for artificial sweeteners and natural sugars Consequently, the transient receptor potential cation channel subfamily M member 5 is activated, thereby increasing intracellular calcium and neurotransmitter release — As artificial sweeteners and natural sugars bind differently to the sweet taste receptors, the gustatory branch is activated differently as well 19 , Thereupon, artificial sweeteners may generate weaker signals that are sent to areas involved in reward and satisfaction, as consistently demonstrated by using functional Magnetic Resonance Imaging fMRI in several randomized cross-over trials , Likewise, the ingestion of artificial sweeteners induces a signaling cascade outside of the oral cavity.

Within the GI tract, sweet taste receptors are primarily located on enteroendocrine L- and K-cells The signal transduction pathway is similar as in cells present in the oral cavity.

These hormones are able to cross the semi-permeable blood-brain barrier, thereby reaching the hypothalamus and affecting food intake by reducing appetite and increasing satiety However, artificial sweeteners may not be potent secretagogues for GLP-1, PYY, and GIP to the same extent in vivo as natural sugars, since the secretion is nutrient-dependent 39 , , For instance, aspartame is digested and absorbed before reaching the lower GI tract to bind to the sweet taste receptors.

Acesulfame-K, sucralose, steviol glycoside, and saccharin pass through the lower GI tract to be absorbed, digested or eliminated directly. Consistently, mice studies and human crossover trials in lean and obese individuals have shown no significant effects of artificial sweeteners on incretin secretion 39 , 40 , 42 , 51 — 53 , , In addition to the lack of an effect on incretin secretion, two human crossover studies showed no effect on appetite upon sucralose or aspartame-sweetened diet coke consumption in healthy and obese individuals 40 , Furthermore, randomized cross-over trials showed weaker reward and satisfaction signals upon aspartame or sucralose ingestion in healthy individuals, thereby suggesting that caloric intake is required in evoking a hypothalamic response , Therefore, it has been suggested that artificial sweeteners do not activate the food reward pathways in the same way as natural sugars.

The elimination of the post-ingestive reward holds true for non-caloric artificial sweeteners, whereas the intake of artificial sweeteners in the presence of carbohydrates may elicit post-ingestive incretin responses, as demonstrated using sucralose-sweetened beverages Based on the above, it can be postulated that artificial sweeteners solely offer less reward compared to natural sugars, although it should be emphasized that the differences in reward response has not been shown in the context of a whole-meal approach or diets, where sugar was replaced by artificial sweeteners.

The lack in complete satisfaction may drive the assumption that artificial sweeteners fuel food seeking behavior, thereby contributing to increased or no differences in energy intake. However, less satisfaction does not necessarily translate into compensatory excess energy intake — RCTs have shown that the reduced caloric intake by replacing natural sugars with artificial sweeteners is not completely compensated , As a result, energy intake after the use of artificial sweeteners is still lower compared to natural sugars, even after putative compensatory energy intake.

Therefore, the compensatory energy intake does not seem to pose a threat to weight gain and may aid in weight loss maintenance. In a meta-analysis of long-term RCTs 4 weeks to 40 months , artificial sweeteners were found to decrease energy intake compared to caloric sweeteners or water