Are artificial sweeteners bad for you?
Despite decades of research attempting to answer this question, most experts aren’t sure.
Some say they’re benign or even somewhat beneficial if they’re substituted for caloric sweeteners like sugar.
Others claim even the tiniest amounts (like that found in a stick of sugar-free gum) pose a serious health risk.
In this article, we’ll look at what science says about the health effects of eating artificial sweeteners, so you can decide for yourself whether you should consume them.
What Are Artificial Sweeteners?
Artificial sweeteners, also known as “sugar substitutes” or “high-intensity sweeteners,” are chemicals used to sweeten foods.
They come in two types: Nutritive and non-nutritive sweeteners. Nutritive sweeteners contain calories, while non-nutritive sweeteners contain few or no calories.
Artificial sweeteners are far sweeter than table sugar (up to 20,000 times sweeter), which means you only need to use a tiny amount to achieve a similar level of sweetness.
There are six FDA-approved artificial sweeteners:
- Advantame: Advantame is approximately 20,000 times sweeter than sugar and contains no calories.
- Acesulfame potassium: Acesulfame potassium (also called acesulfame K, acesulfame potassium, or Ace-K) is sold under the brand names Sunett and Sweet One. It’s ~200 times sweeter than sugar, contains no calories, and is often combined with other sweeteners.
- Aspartame: Aspartame brand names include Nutrasweet, Equal, and Sugar Twin. It’s ~200 times sweeter than sugar and contains 4 calories per gram.
- Neotame: Neotame is sold under the brand name Newtame, is ~7,000-to-13,000 times sweeter than sugar, and contains no calories.
- Saccharin: Saccharin brand names include Sweet and Low, Sweet Twin, Sweet’N Low, and Necta Sweet. It’s ~200-to-700 times sweeter than sugar and contains no calories.
- Sucralose: Sucralose is sold under the brand name Splenda, is ~600 times sweeter than sugar, and contains no calories.
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Are Artificial Sweeteners Bad for You?
People fear that artificial sweeteners harm health in many ways, but the most common concerns are that they cause cancer, diabetes, and weight gain and damage your gut health.
Let’s look at what science says about each of these worries.
Artificial Sweeteners and Cancer
The fear that artificial sweeteners cause cancer dates back to 1970 when a study showed that mice that consumed huge amounts of saccharin and cyclamate (an artificial sweetener that the U.S. regulatory authority subsequently banned) had an increased risk of bladder cancer.
Over the following decades, multiple studies showing no link between artificial sweeteners and cancer risk in humans tempered these concerns.
Recently, a large cohort study conducted by scientists at Sorbonne Paris Nord University rewakened this worry when it found that people who consume artificial sweeteners (particularly aspartame and acesulfame-K) had a higher risk of cancer than those who didn’t.
While a cursory glance at these results paints an unsettling picture, a more thorough reading uncovers a couple of reasons to be wary of the findings.
First, it was an observational study, which means it can only show that artificial sweeteners and cancer are correlated, not that one causes the other.
Given that the artificial sweetener consumers with the highest cancer risk were also more likely to smoke, be less physically active, have diabetes, and eat less fruit, fiber, vegetables, and whole grains and more salt and sugar than those who didn’t eat artificial sweeteners, other confounding variables likely contributed to their higher cancer risk.
Second, the researchers found that people who ate artificial sweeteners in small amounts had a higher cancer risk than those who ate them in large amounts. This is strange since if artificial sweeteners “cause” cancer, you’d expect to see a dose-response relationship, where the more you eat, the higher your risk of cancer—but this isn’t the case.
It’s also worth putting the findings of this study into perspective.
Based on the findings, many media outlets reported that artificial sweeteners “increase cancer risk by 13%,” which is a scary thought. This isn’t exactly what the study found, though.
The results actually showed that people who consume artificial sweeteners have a 13% relative increase in cancer risk compared to those who don’t. A relative increase, however, isn’t the same as an absolute increase.
For example, if you usually have a 5% risk of cancer, and you eat artificial sweeteners, causing a relative increase in cancer risk by 13%, your overall cancer risk is now 5.65% (your overall cancer risk would only jump to 18% if it were an absolute increase).
In other words, even if we were to take these results at face value, the effect of artificial sweeteners on cancer risk is relatively small—smaller than the effect of eating red meat on cancer risk, according to some research.
At bottom, most studies suggest there’s no link between artificial sweetener intake and cancer, and those indicating otherwise show that any risk is negligible. As such, it’s probably safe to conclude that artificial sweeteners have either no or minimal effect on cancer risk.
Artificial Sweeteners and Diabetes
While there appears to be an association between artificial sweeteners and diabetes, we don’t yet understand whether artificial sweeteners contribute to or help prevent diabetes.
For instance, several studies have shown that artificial sweeteners don’t raise blood sugar or insulin levels in humans. This is typically beneficial for metabolic health (and thus diabetes risk) since maintaining relatively low blood sugar and insulin levels is generally better than having high levels.
Conversely, several observational studies have linked consuming artificial sweeteners with an increased risk of developing type 2 diabetes.
Again, observational studies can’t tell us that artificial sweeteners cause diabetes, only that people who develop diabetes also regularly consume artificial sweeteners. Nonetheless, this suggests a connection between consuming artificial sweeteners and diabetes risk.
Animal research muddies the waters further.
Some studies on rodents and animal cells show that artificial sweeteners “disrupt” the gut microbiome (the microbes in your intestines), triggering the release of inflammatory proteins that interfere with insulin’s ability to remove glucose from the blood, which could lead to insulin resistance and diabetes.
Others, however, show that rats given artificial sweeteners produce more short-chain fatty acids.
Short-chain fatty acids are compounds produced by the “friendly bacteria” in your gut that are crucial for maintaining optimal metabolic and intestinal health and that may increase fat burning, limit fat storage, and fight inflammation, all of which can help you avert diabetes.
Since most human research suggests that artificially sweetened food and drinks are generally better for metabolic health than sugary alternatives, it’s likely safe to consume them in moderation.
Still, we need more long-term human research before we can definitively say that artificial sweeteners positively affect diabetes risk.
This is really the biggest rub with artificial sweeteners: we just aren’t sure what the long-term effects are for all of them.
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Artificial Sweeteners and Weight Gain
Artificially sweetened food and drinks typically contain fewer calories than sugary alternatives, so many people use them to aid weight loss. Research on how artificial sweeteners affect body weight isn’t always clear, though.
For example, while there’s evidence that artificial sweeteners increase your appetite and cravings for sweet treats and thus contribute to weight gain, other research shows that people who substitute sugar-sweetened food and drinks with artificially sweetened fare feel less hungry, eat fewer calories, and find losing weight easier.
What’s more, multiple observational studies have uncovered a link between consuming artificial sweeteners and obesity. However, most randomized controlled trials (the “gold standard” of scientific research) show consuming artificial sweeteners in place of sugar aids fat loss.
Given the results of the highest-quality research, it’s safe to assume that artificial sweeteners aid weight loss for most people.
Artificial Sweeteners and Gut Health
Your gut microbiome and the fermented products it creates are key to numerous aspects of your health, including your body weight, insulin sensitivity, metabolic health, immune function, and sleep.
Most human and animal studies show that artificial sweeteners alter the composition of your gut microbiome, which means they could affect your health—though not necessarily negatively.
For example, as we’ve already seen, artificial sweeteners increase short-chain fatty acid production. While research suggests this reduces appetite and increases calorie and fat burning in animals, some human research has tentatively linked it to obesity. One way it might do this is by enabling the body to “extract” more energy (calories) from foods that would otherwise pass through your body undigested.
That said, other human and human cell studies have found that short-chain fatty acids may regulate appetite and increase energy expenditure. This would likely improve body weight and thus insulin sensitivity and metabolic health.
There are three more studies in living humans worth mentioning.
In one, researchers found that the gut microbiome of 4 out of 7 healthy people changed after consuming large amounts of saccharin, which inhibited how their bodies’ controlled blood sugar for as long as 7 days after the trial.
In another, researchers found that saccharin, sucralose, aspartame, and stevia altered the gut microbiome in healthy people, and that saccharin and sucralose elevated blood sugar levels.
And in the last, researchers found that feeding people large amounts of saccharin had no effect on the gut microbiome or blood sugar control.
Given the conflicting evidence, it’s too early to say whether artificial sweeteners damage gut health or not. Until scientists conduct more research in humans, the safest bet is to consume artificial sweeteners in moderation or not at all.
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Research on how artificial sweeteners affect human health is still early days, so it’s hard to draw firm conclusions about their long-term effects.
That said, current evidence suggests that artificial sweeteners aren’t the health hazard many claim they are. If they increased disease risk and ruined our metabolic health the way some suppose, long-term trials probably would have served up more hints this is the case—but they haven’t.
In most cases, studies report negligible effects on metabolic health, with some suggesting artificial sweeteners offer some benefits.
Still, there are plenty of tip-offs in the literature to suggest artificial sweeteners aren’t all good. Thus, the best thing to do for now is to consume them in moderation or not at all.
It’s also important to remember that every artificial sweetener is a unique molecule with its own effects on the body. Just because one artificial sweetener is proven to be relatively safe or unsafe doesn’t mean you can apply those findings to the rest of them.
In other words, you need to look at each one individually when deciding what the risks and benefits are.
+ Scientific References
- Ronai, P. (2019). Do It Right: The Seated Cable Row Exercise. ACSM’s Health and Fitness Journal, 23(4), 32–37. https://doi.org/10.1249/FIT.0000000000000492
- Graham, J. F. B. C. D. (n.d.). Dumbbell One-Arm Row : Strength & Conditioning Journal. Retrieved December 12, 2022, from https://journals.lww.com/nsca-scj/Citation/2001/04000/Dumbbell_One_Arm_Row.14.aspx
- Jakobi, J. M., & Chilibeck, P. D. (2001). Bilateral and unilateral contractions: possible differences in maximal voluntary force. Canadian Journal of Applied Physiology = Revue Canadienne de Physiologie Appliquee, 26(1), 12–33. https://doi.org/10.1139/H01-002
- Janzen, C. L., Chilibeck, P. D., & Davison, K. S. (2006). The effect of unilateral and bilateral strength training on the bilateral deficit and lean tissue mass in post-menopausal women. European Journal of Applied Physiology 2006 97:3, 97(3), 253–260. https://doi.org/10.1007/S00421-006-0165-1
- Liao, K. F., Nassis, G. P., Bishop, C., Yang, W., Bian, C., & Li, Y. M. (2021). Effects of unilateral vs. bilateral resistance training interventions on measures of strength, jump, linear and change of direction speed: a systematic review and meta-analysis. Biology of Sport, 39(3), 485–497. https://doi.org/10.5114/BIOLSPORT.2022.107024
- Schoenfeld, B. J. (2010). The mechanisms of muscle hypertrophy and their application to resistance training. Journal of Strength and Conditioning Research, 24(10), 2857–2872. https://doi.org/10.1519/JSC.0B013E3181E840F3
- Fenwick, C. M. J., Brown, S. H. M., & Mcgill, S. M. (2009). Comparison of different rowing exercises: trunk muscle activation and lumbar spine motion, load, and stiffness. Journal of Strength and Conditioning Research, 23(2), 350–358. https://doi.org/10.1519/JSC.0B013E3181942019
- Ronai, P. (2017). The Barbell Row Exercise. ACSM’s Health and Fitness Journal, 21(2), 25–28. https://doi.org/10.1249/FIT.0000000000000278
- Sharma, A., Amarnath, S., Thulasimani, M., & Ramaswamy, S. (2016). Artificial sweeteners as a sugar substitute: Are they really safe? Indian Journal of Pharmacology, 48(3), 237. https://doi.org/10.4103/0253-7613.182888
- Sclafani, A., & Ackroff, K. (2015). Advantame Sweetener Preference in C57BL/6J Mice and Sprague-Dawley Rats. Chemical Senses, 40(3), 181. https://doi.org/10.1093/CHEMSE/BJU070
- Price, J. M., Biava, C. G., Oser, B. L., Vogin, E. E., Steinfeld, J., & Ley, H. L. (1970). Bladder tumors in rats fed cyclohexylamine or high doses of a mixture of cyclamate and saccharin. Science (New York, N.Y.), 167(3921), 1131–1132. https://doi.org/10.1126/SCIENCE.167.3921.1131
- Gallus, S., Scotti, L., Negri, E., Talamini, R., Franceschi, S., Montella, M., Giacosa, A., Dal Maso, L., & La Vecchia, C. (2007). Artificial sweeteners and cancer risk in a network of case-control studies. Annals of Oncology : Official Journal of the European Society for Medical Oncology, 18(1), 40–44. https://doi.org/10.1093/ANNONC/MDL346
- Bosetti, C., Gallus, S., Talamini, R., Montella, M., Franceschi, S., Negri, E., & La Vecchia, C. (2009). Artificial sweeteners and the risk of gastric, pancreatic, and endometrial cancers in Italy. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 18(8), 2235–2238. https://doi.org/10.1158/1055-9965.EPI-09-0365
- Magnuson, B. A., Burdock, G. A., Doull, J., Kroes, R. M., Marsh, G. M., Pariza, M. W., Spencer, P. S., Waddell, W. J., Walker, R., & Williams, G. M. (2007). Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Critical Reviews in Toxicology, 37(8), 629–727. https://doi.org/10.1080/10408440701516184
- Marinovich, M., Galli, C. L., Bosetti, C., Gallus, S., & La Vecchia, C. (2013). Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 60, 109–115. https://doi.org/10.1016/J.FCT.2013.07.040
- Mishra, A., Ahmed, K., Froghi, S., & Dasgupta, P. (2015). Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants. International Journal of Clinical Practice, 69(12), 1418–1426. https://doi.org/10.1111/IJCP.12703
- Kroger, M., Meister, K., & Kava, R. (2006). Low-calorie Sweeteners and Other Sugar Substitutes: A Review of the Safety Issues. Comprehensive Reviews in Food Science and Food Safety, 5(2), 35–47. https://doi.org/10.1111/J.1541-4337.2006.TB00081.X
- Debras, C., Chazelas, E., Srour, B., Druesne-Pecollo, N., Esseddik, Y., de Edelenyi, F. S., Agaësse, C., De Sa, A., Lutchia, R., Gigandet, S., Huybrechts, I., Julia, C., Kesse-Guyot, E., Allès, B., Andreeva, V. A., Galan, P., Hercbergi, S., Deschasaux-Tanguy, M., & Touvier, M. (2022). Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Medicine, 19(3). https://doi.org/10.1371/JOURNAL.PMED.1003950
- Farvid, M. S., Sidahmed, E., Spence, N. D., Mante Angua, K., Rosner, B. A., & Barnett, J. B. (2021). Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. European Journal of Epidemiology, 36(9), 937–951. https://doi.org/10.1007/S10654-021-00741-9
- Carlson, H. E., & Shah, J. H. (1989). Aspartame and its constituent amino acids: effects on prolactin, cortisol, growth hormone, insulin, and glucose in normal humans. The American Journal of Clinical Nutrition, 49(3), 427–432. https://doi.org/10.1093/AJCN/49.3.427
- Ma, J., Bellon, M., Wishart, J. M., Young, R., Blackshaw, L. A., Jones, K. L., Horowitz, M., & Rayner, C. K. (2009). Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. American Journal of Physiology. Gastrointestinal and Liver Physiology, 296(4). https://doi.org/10.1152/AJPGI.90708.2008
- Horwitz, D. L., McLane, M., & Kobe, P. (1988). Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care, 11(3), 230–234. https://doi.org/10.2337/DIACARE.11.3.230
- Ma, J., Chang, J., Checklin, H. L., Young, R. L., Jones, K. L., Horowitz, M., & Rayner, C. K. (2010). Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. The British Journal of Nutrition, 104(6), 803–806. https://doi.org/10.1017/S0007114510001327
- Ford, H. E., Peters, V., Martin, N. M., Sleeth, M. L., Ghatei, M. A., Frost, G. S., & Bloom, S. R. (2011). Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. European Journal of Clinical Nutrition, 65(4), 508–513. https://doi.org/10.1038/EJCN.2010.291
- Tey, S. L., Salleh, N. B., Henry, J., & Forde, C. G. (2017). Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. International Journal of Obesity (2005), 41(3), 450–457. https://doi.org/10.1038/IJO.2016.225
- Mouri, Mi., & Badireddy, M. (2022). Hyperglycemia. Mader’s Reptile and Amphibian Medicine and Surgery, 1314-1315.e1. https://doi.org/10.1016/B978-0-323-48253-0.00155-0
- Kolb, H., Kempf, K., Röhling, M., & Martin, S. (2020). Insulin: Too much of a good thing is bad. BMC Medicine, 18(1), 1–12. https://doi.org/10.1186/S12916-020-01688-6/TABLES/1
- Nettleton, J. A., Lutsey, P. L., Wang, Y., Lima, J. A., Michos, E. D., & Jacobs, D. R. (2009). Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care, 32(4), 688–694. https://doi.org/10.2337/DC08-1799
- Fagherazzi, G., Vilier, A., Sartorelli, D. S., Lajous, M., Balkau, B., & Clavel-Chapelon, F. (2013). Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort. The American Journal of Clinical Nutrition, 97(3), 517–523. https://doi.org/10.3945/AJCN.112.050997
- Mathur, K., Agrawal, R. K., Nagpure, S., & Deshpande, D. (2020). Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients. Journal of Family Medicine and Primary Care, 9(1), 69. https://doi.org/10.4103/JFMPC.JFMPC_329_19
- Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., & Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014 514:7521, 514(7521), 181–186. https://doi.org/10.1038/nature13793
- Bian, X., Tu, P., Chi, L., Gao, B., Ru, H., & Lu, K. (2017). Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 107(Pt B), 530–539. https://doi.org/10.1016/J.FCT.2017.04.045
- Santos, P. S., Caria, C. R. P., Gotardo, E. M. F., Ribeiro, M. L., Pedrazzoli, J., & Gambero, A. (2018). Artificial sweetener saccharin disrupts intestinal epithelial cells’ barrier function in vitro. Food & Function, 9(7), 3815–3822. https://doi.org/10.1039/C8FO00883C
- Stienstra, R., Tack, C. J., Kanneganti, T. D., Joosten, L. A. B., & Netea, M. G. (2012). The inflammasome puts obesity in the danger zone. Cell Metabolism, 15(1), 10–18. https://doi.org/10.1016/J.CMET.2011.10.011
- Rotter, V., Nagaev, I., & Smith, U. (2003). Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. The Journal of Biological Chemistry, 278(46), 45777–45784. https://doi.org/10.1074/JBC.M301977200
- Jager, J., Grémeaux, T., Cormont, M., Le Marchand-Brustel, Y., & Tanti, J. F. (2007). Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology, 148(1), 241–251. https://doi.org/10.1210/EN.2006-0692
- Steensels, S., Cools, L., Avau, B., Vancleef, L., Farré, R., Verbeke, K., & Depoortere, I. (2017). Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release. Molecular Nutrition & Food Research, 61(3). https://doi.org/10.1002/MNFR.201600716
- Uebanso, T., Ohnishi, A., Kitayama, R., Yoshimoto, A., Nakahashi, M., Shimohata, T., Mawatari, K., & Takahashi, A. (2017). Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice. Nutrients, 9(6), 560. https://doi.org/10.3390/NU9060560
- Nettleton, J. E., Klancic, T., Schick, A., Choo, A. C., Shearer, J., Borgland, S. L., Chleilat, F., Mayengbam, S., & Reimer, R. A. (2019). Low-Dose Stevia (Rebaudioside A) Consumption Perturbs Gut Microbiota and the Mesolimbic Dopamine Reward System. Nutrients, 11(6). https://doi.org/10.3390/NU11061248
- Ríos-Covián, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., De los Reyes-Gavilán, C. G., & Salazar, N. (2016). Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Frontiers in Microbiology, 7(FEB). https://doi.org/10.3389/FMICB.2016.00185
- Canfora, E. E., Jocken, J. W., & Blaak, E. E. (2015). Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews Endocrinology 2015 11:10, 11(10), 577–591. https://doi.org/10.1038/nrendo.2015.128
- Hernández, M. A. G., Canfora, E. E., Jocken, J. W. E., & Blaak, E. E. (2019). The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients, 11(8). https://doi.org/10.3390/NU11081943
- He, J., Zhang, P., Shen, L., Niu, L., Tan, Y., Chen, L., Zhao, Y., Bai, L., Hao, X., Li, X., Zhang, S., & Zhu, L. (2020). Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. International Journal of Molecular Sciences, 21(17), 1–16. https://doi.org/10.3390/IJMS21176356
- Liu, T., Li, J., Liu, Y., Xiao, N., Suo, H., Xie, K., Yang, C., & Wu, C. (2012). Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation, 35(5), 1676–1684. https://doi.org/10.1007/S10753-012-9484-Z
- Daher, M. I., Matta, J. M., & Abdel Nour, A. M. (2019). Non-nutritive sweeteners and type 2 diabetes: Should we ring the bell? Diabetes Research and Clinical Practice, 155. https://doi.org/10.1016/J.DIABRES.2019.107786
- Cui, M., Jiang, P., Maillet, E., Max, M., Margolskee, R., & Osman, R. (2006). The heterodimeric sweet taste receptor has multiple potential ligand binding sites. Current Pharmaceutical Design, 12(35), 4591–4600. https://doi.org/10.2174/138161206779010350
- Haase, L., Cerf-Ducastel, B., & Murphy, C. (2009). Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety. NeuroImage, 44(3), 1008–1021. https://doi.org/10.1016/J.NEUROIMAGE.2008.09.044
- Lavin, J. H., French, S. J., & Read, N. W. (1997). The effect of sucrose- and aspartame-sweetened drinks on energy intake, hunger and food choice of female, moderately restrained eaters. International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity, 21(1), 37–42. https://doi.org/10.1038/SJ.IJO.0800360
- Tordoff, M. G., & Alleva, A. M. (1990). Oral stimulation with aspartame increases hunger. Physiology & Behavior, 47(3), 555–559. https://doi.org/10.1016/0031-9384(90)90126-O
- Peters, J. C., Wyatt, H. R., Foster, G. D., Pan, Z., Wojtanowski, A. C., Vander Veur, S. S., Herring, S. J., Brill, C., & Hill, J. O. (2014). The effects of water and non-nutritive sweetened beverages on weight loss during a 12-week weight loss treatment program. Obesity (Silver Spring, Md.), 22(6), 1415–1421. https://doi.org/10.1002/OBY.20737
- Piernas, C., Tate, D. F., Wang, X., & Popkin, B. M. (2013). Does diet-beverage intake affect dietary consumption patterns? Results from the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. The American Journal of Clinical Nutrition, 97(3), 604–611. https://doi.org/10.3945/AJCN.112.048405
- Raben, A., Vasilaras, T. H., Christina Møller, A., & Astrup, A. (2002). Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. The American Journal of Clinical Nutrition, 76(4), 721–729. https://doi.org/10.1093/AJCN/76.4.721
- Anton, S. D., Martin, C. K., Han, H., Coulon, S., Cefalu, W. T., Geiselman, P., & Williamson, D. A. (2010). Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite, 55(1), 37. https://doi.org/10.1016/J.APPET.2010.03.009
- Crézé, C., Candal, L., Cros, J., Knebel, J. F., Seyssel, K., Stefanoni, N., Schneiter, P., Murray, M. M., Tappy, L., & Toepel, U. (2018). The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans. Nutrients, 10(5). https://doi.org/10.3390/NU10050615
- Colditz, G. A., Willett, W. C., Stampfer, M. J., London, S. J., Segal, M. R., & Speizer, F. E. (1990). Patterns of weight change and their relation to diet in a cohort of healthy women. The American Journal of Clinical Nutrition, 51(6), 1100–1105. https://doi.org/10.1093/AJCN/51.6.1100
- Fowler, S. P., Williams, K., Resendez, R. G., Hunt, K. J., Hazuda, H. P., & Stern, M. P. (2008). Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring, Md.), 16(8), 1894–1900. https://doi.org/10.1038/OBY.2008.284
- Stellman, S. D., & Garfinkel, L. (1986). Artificial sweetener use and one-year weight change among women. Preventive Medicine, 15(2), 195–202. https://doi.org/10.1016/0091-7435(86)90089-7
- Azad, M. B., Sharma, A. K., De Souza, R. J., Dolinsky, V. W., Becker, A. B., Mandhane, P. J., Turvey, S. E., Subbarao, P., Lefebvre, D. L., Sears, M. R., Anand, S., Cyr, M., Denburg, J. A., Larché, M., Macri, J., Dell, S., Grasemann, H., Hegele, R., Moraes, T. J., … Laprise, C. (2016). Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. JAMA Pediatrics, 170(7), 662–670. https://doi.org/10.1001/JAMAPEDIATRICS.2016.0301
- Chia, C. W., Shardell, M., Tanaka, T., Liu, D. D., Gravenstein, K. S., Simonsick, E. M., Egan, J. M., & Ferrucci, L. (2016). Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older Adults: A Cohort Study. PLOS ONE, 11(11), e0167241. https://doi.org/10.1371/JOURNAL.PONE.0167241
- Rogers, P. J., Hogenkamp, P. S., De Graaf, C., Higgs, S., Lluch, A., Ness, A. R., Penfold, C., Perry, R., Putz, P., Yeomans, M. R., & Mela, D. J. (2016). Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. International Journal of Obesity (2005), 40(3), 381. https://doi.org/10.1038/IJO.2015.177
- Miller, P. E., & Perez, V. (2014). Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. The American Journal of Clinical Nutrition, 100(3), 765–777. https://doi.org/10.3945/AJCN.113.082826
- Fernstrom, J. D. (2015). Non-nutritive sweeteners and obesity. Annual Review of Food Science and Technology, 6, 119–136. https://doi.org/10.1146/ANNUREV-FOOD-022814-015635
- Wiebe, N., Padwal, R., Field, C., Marks, S., Jacobs, R., & Tonelli, M. (2011). A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. BMC Medicine, 9. https://doi.org/10.1186/1741-7015-9-123
- de la Hunty, A., Gibson, S., & Ashwell, M. (2006). A review of the effectiveness of aspartame in helping with weight control. Nutrition Bulletin, 31(2), 115–128. https://doi.org/10.1111/J.1467-3010.2006.00564.X
- Yang, Q. (2010). Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. The Yale Journal of Biology and Medicine, 83(2), 101. /pmc/articles/PMC2892765/
- Canfora, E. E., Meex, R. C. R., Venema, K., & Blaak, E. E. (2019). Gut microbial metabolites in obesity, NAFLD and T2DM. Nature Reviews. Endocrinology, 15(5), 261–273. https://doi.org/10.1038/S41574-019-0156-Z
- Jandhyala, S. M., Talukdar, R., Subramanyam, C., Vuyyuru, H., Sasikala, M., & Reddy, D. N. (2015). Role of the normal gut microbiota. World Journal of Gastroenterology, 21(29), 8836–8847. https://doi.org/10.3748/WJG.V21.I29.8787
- Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027–1031. https://doi.org/10.1038/NATURE05414
- Wang, J., Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., … Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55–60. https://doi.org/10.1038/NATURE11450
- Janssen, A. W. F., & Kersten, S. (2015). The role of the gut microbiota in metabolic health. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 29(8), 3111–3123. https://doi.org/10.1096/FJ.14-269514
- Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012). The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell, 148(6), 1258. https://doi.org/10.1016/J.CELL.2012.01.035
- Leone, V., Gibbons, S. M., Martinez, K., Hutchison, A. L., Huang, E. Y., Cham, C. M., Pierre, J. F., Heneghan, A. F., Nadimpalli, A., Hubert, N., Zale, E., Wang, Y., Huang, Y., Theriault, B., Dinner, A. R., Musch, M. W., Kudsk, K. A., Prendergast, B. J., Gilbert, J. A., & Chang, E. B. (2015). Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host & Microbe, 17(5), 681–689. https://doi.org/10.1016/J.CHOM.2015.03.006
- Turnbaugh, P. J., Bäckhed, F., Fulton, L., & Gordon, J. I. (2008). Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host & Microbe, 3(4), 213–223. https://doi.org/10.1016/J.CHOM.2008.02.015
- Farup, P. G., Lydersen, S., & Valeur, J. (2019). Are Nonnutritive Sweeteners Obesogenic? Associations between Diet, Faecal Microbiota, and Short-Chain Fatty Acids in Morbidly Obese Subjects. Journal of Obesity, 2019. https://doi.org/10.1155/2019/4608315
- Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., & Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181–186. https://doi.org/10.1038/NATURE13793
- Frankenfeld, C. L., Sikaroodi, M., Lamb, E., Shoemaker, S., & Gillevet, P. M. (2015). High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Annals of Epidemiology, 25(10), 736-742.e4. https://doi.org/10.1016/J.ANNEPIDEM.2015.06.083
- Wang, Q. P., Browman, D., Herzog, H., & Gregory Neely, G. (2018). Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PloS One, 13(7). https://doi.org/10.1371/JOURNAL.PONE.0199080
- De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., & Mithieux, G. (2014). Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell, 156(1–2), 84–96. https://doi.org/10.1016/J.CELL.2013.12.016
- Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009). Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes, 58(7), 1509–1517. https://doi.org/10.2337/DB08-1637
- Lin, H. V., Frassetto, A., Kowalik, E. J., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., & Marsh, D. J. (2012). Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PloS One, 7(4). https://doi.org/10.1371/JOURNAL.PONE.0035240
- Frost, G., Sleeth, M. L., Sahuri-Arisoylu, M., Lizarbe, B., Cerdan, S., Brody, L., Anastasovska, J., Ghourab, S., Hankir, M., Zhang, S., Carling, D., Swann, J. R., Gibson, G., Viardot, A., Morrison, D., Thomas, E. L., & Bell, J. D. (2014). The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications 2014 5:1, 5(1), 1–11. https://doi.org/10.1038/ncomms4611
- Den Besten, G., Bleeker, A., Gerding, A., Van Eunen, K., Havinga, R., Van Dijk, T. H., Oosterveer, M. H., Jonker, J. W., Groen, A. K., Reijngoud, D. J., & Bakker, B. M. (2015). Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation. Diabetes, 64(7), 2398–2408. https://doi.org/10.2337/DB14-1213
- Fernandes, J., Su, W., Rahat-Rozenbloom, S., Wolever, T. M. S., & Comelli, E. M. (2014). Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutrition & Diabetes, 4(6), e121. https://doi.org/10.1038/NUTD.2014.23
- Zhao, L. (2013). The gut microbiota and obesity: from correlation to causality. Nature Reviews. Microbiology, 11(9), 639–647. https://doi.org/10.1038/NRMICRO3089
- Hartstra, A. V., Bouter, K. E. C., Bäckhed, F., & Nieuwdorp, M. (2015). Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care, 38(1), 159–165. https://doi.org/10.2337/DC14-0769
- Chambers, E. S., Viardot, A., Psichas, A., Morrison, D. J., Murphy, K. G., Zac-Varghese, S. E. K., MacDougall, K., Preston, T., Tedford, C., Finlayson, G. S., Blundell, J. E., Bell, J. D., Thomas, E. L., Mt-Isa, S., Ashby, D., Gibson, G. R., Kolida, S., Dhillo, W. S., Bloom, S. R., … Frost, G. (2015). Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut, 64(11), 1744–1754. https://doi.org/10.1136/GUTJNL-2014-307913/-/DC1
- Alhabeeb, H., Chambers, E. S., Frost, G., Morrison, D. J., & Preston, T. (2014). Inulin propionate ester increases satiety and decreases appetite but does not affect gastric emptying in healthy humans. Proceedings of the Nutrition Society, 73(OCE1), E21. https://doi.org/10.1017/S0029665114000354
- Larraufie, P., Martin-Gallausiaux, C., Lapaque, N., Dore, J., Gribble, F. M., Reimann, F., & Blottiere, H. M. (2018). SCFAs strongly stimulate PYY production in human enteroendocrine cells. Scientific Reports 2017 8:1, 8(1), 1–9. https://doi.org/10.1038/s41598-017-18259-0
- Reimer, R. A., Darimont, C., Gremlich, S., Nicolas-Métral, V., Rüegg, U. T., & Macé, K. (2001). A human cellular model for studying the regulation of glucagon-like peptide-1 secretion. Endocrinology, 142(10), 4522–4528. https://doi.org/10.1210/ENDO.142.10.8415
- Tolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., & Gribble, F. M. (2012). Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes, 61(2), 364–371. https://doi.org/10.2337/DB11-1019
- Al-Lahham, S. H., Roelofsen, H., Priebe, M., Weening, D., Dijkstra, M., Hoek, A., Rezaee, F., Venema, K., & Vonk, R. J. (2010). Regulation of adipokine production in human adipose tissue by propionic acid. European Journal of Clinical Investigation, 40(5), 401–407. https://doi.org/10.1111/J.1365-2362.2010.02278.X
- Canfora, E. E., Van Der Beek, C. M., Jocken, J. W. E., Goossens, G. H., Holst, J. J., Olde Damink, S. W. M., Lenaerts, K., Dejong, C. H. C., & Blaak, E. E. (2017). Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Scientific Reports, 7(1). https://doi.org/10.1038/S41598-017-02546-X
- Suez, J., Cohen, Y., Valdés-Mas, R., Mor, U., Dori-Bachash, M., Federici, S., Zmora, N., Leshem, A., Heinemann, M., Linevsky, R., Zur, M., Ben-Zeev Brik, R., Bukimer, A., Eliyahu-Miller, S., Metz, A., Fischbein, R., Sharov, O., Malitsky, S., Itkin, M., … Elinav, E. (2022). Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell, 185(18), 3307-3328.e19. https://doi.org/10.1016/J.CELL.2022.07.016
- Serrano, J., Smith, K. R., Crouch, A. L., Sharma, V., Yi, F., Vargova, V., LaMoia, T. E., Dupont, L. M., Serna, V., Tang, F., Gomes-Dias, L., Blakeslee, J. J., Hatzakis, E., Peterson, S. N., Anderson, M., Pratley, R. E., & Kyriazis, G. A. (2021). High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome, 9(1), 1–18. https://doi.org/10.1186/S40168-020-00976-W/FIGURES/4
- McGlynn, N. D., Khan, T. A., Wang, L., Zhang, R., Chiavaroli, L., Au-Yeung, F., Lee, J. J., Noronha, J. C., Comelli, E. M., Blanco Mejia, S., Ahmed, A., Malik, V. S., Hill, J. O., Leiter, L. A., Agarwal, A., Jeppesen, P. B., Rahelić, D., Kahleová, H., Salas-Salvadó, J., … Sievenpiper, J. L. (2022). Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Network Open, 5(3). https://doi.org/10.1001/JAMANETWORKOPEN.2022.2092
- Lohner, S., Kuellenberg de Gaudry, D., Toews, I., Ferenci, T., & Meerpohl, J. J. (2020). Non-nutritive sweeteners for diabetes mellitus. The Cochrane Database of Systematic Reviews, 5(5). https://doi.org/10.1002/14651858.CD012885.PUB2
- Pang, M. D., Goossens, G. H., & Blaak, E. E. (2021). The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis. Frontiers in Nutrition, 7. https://doi.org/10.3389/FNUT.2020.598340