ARTIFICIAL SWEETENERS: WHAT DOES THE EVIDENCE SAY?

Over recent years the topic of artificial sweeteners has been a controversial affair. 

On one hand, artificial sweeteners are considered safe for use by major health authorities (1) and are considered to be physiologically inactive in the body, and are also widely used as a weight loss strategy and to reduce added sugar intake.

On the other hand, it has been argued that artificial sweeteners may in fact have an influence on blood sugar and appetite (2).

Overall, the scientific evidence for the effects of artificial sweeteners on health is inconclusive. 

What are they?

Artificial sweeteners are synthetic sugar substitutes that are added to foods and drinks to provide a sweet taste. 

They are typically found in products such as “diet” drinks and “sugar-free” condiments as well as in a variety of grains, snack foods, yoghurts, desserts, sweetened milks and breakfast cereals, which many shoppers often do not realise contain artificial sweeteners (3).

Unlike sugar, artificial sweeteners contain very little or no calories at all, whilst still maintaining the sweetness of the food or drink. 

In fact, most are hundred of times sweeter than sugar, gram for gram; and therefore are often referred to as “intense sweeteners”. 

However, some do contain calories. For example, aspartame contains 4 calories per gram much like sugar, however the quantity required to sweeten a food or drink is so minimal that the calories it provides are negligible (4).

As a result, using artificial sweeteners in place of refined sugar can be an effective way to reduce your calorie intake. 

How do they work?

The tongue and soft palate of your mouth are covered by many taste buds, each containing multiple taste receptors that have the ability to detect different flavours (5).

When consumed, food molecules bind to and activate these taste receptors. A signal is then sent to your brain enabling you to recognise the flavour (5).

For example, much like sugar, artificial sweeteners activate the sweet taste receptor, enabling your brain to perceive its sweet taste. 

In more recent years, it has been discovered that artificial sweeteners also fit with sweet taste receptors found in the gut and the pancreas (6, 7). 

However, they are typically too dissimilar to sugar to be broken down into calories by your body, hence they still taste sweet without the added calories. 

Common Artificial Sweeteners

The most common non-caloric artificial sweeteners are substances with a very intense sweet taste. They can be used in small amounts to replace the sweetness of a far greater amount of sugar.

While multiple different sweeteners exist, not all of them are approved for use in every country. 

The following are artificial sweeteners that are currently approved for use in the United Kingdom and/or the United States, and the brand names by which they are sold under individually (8, 9) - some of which you may recognise:

  • Aspartame - Sunett, Sweet One, Sugar Twin

  • Acesulfame potassium (Acesulfame-K, Ace-K) - NutraSweet, Equal

  • Neotame - Newtame

  • Saccharin - Sweet’N Low, Sugar twin, Sweet Twin

  • Sucralose - Splenda

  • Cyclamate - Sucaryl

  • Alitame - Aclame

Some low-calorie sweeteners are processed from natural ingredients, which means that they are not classed as “artificial”.

These include the natural, zero-calorie sweetener stevia, along with sugar alcohols such as erythritol, sorbitol, xylitol, and mannitol. 

Effects on Appetite 

In theory, saving calories by consuming artificial sweeteners instead of sugar should lead to a net reduction in your total energy intake.

However, research in animals has led some researchers to believe that artificial sweeteners might actually lead to increased appetite and compensation or overcompensation of the ‘saved’ calories, thus promoting weight gain (10).

As artificial sweeteners are sweet but do not contain the calories that sugar does, it has been suggested that this uncoupling of a sweet taste and calories might impede the ability for the body to release the chemicals and hormones it normally would to leave you feeling satisfied after eating (11), therefore in essence “fooling the body” into still feeling hungry. 

Another suggestion is that artificial sweeteners activate the central reward pathway to a lesser extent than sugar (12). Magnetic Resonance Imaging (MRI) scans in 12 women found that sucralose led to a weaker pleasantness response in various regions of the brain than the sugar, sucrose (12). 

This could possibly then lead to increased appetite to eat other sweet foods afterwards. 

Nevertheless, there has recently been multiple short and longer term studies in humans that do not support the idea that artificial sweeteners increase appetite and calorie intake (13,14,15).

In fact, some studies show that replacing sugary drinks and foods with artificially sweetened versions might be beneficial for reducing energy intake (13, 16, 17). 

For example, in a study in 31 adults, consuming drinks sweetened with aspartame (290 kcal) and stevia (290 kcal) before their lunch and dinner meals led to similar levels of hunger and fullness, and food intake at the meals as a sucrose (sugar) sweetened drink (493 kcal) (13). 

But, due to the calorie difference in the drinks, this meant that they in fact consumed less calories in total over the day after the artificially sweetened drinks (13).

Effects on Body Weight 

Some observational studies reported an association between long term artificial sweetener consumption and obesity (18).

For example, a key study reported that people who consumed artificially sweetened drinks were more likely to gain weight over the 7-to-8 year follow up (19). This was reported as a dose response relationship. In other words, the greater amount of diet drinks consumed per week, the greater the amount of weight gain. 

However, it is important to remember that observational studies like this one cannot prove causation but only enable investigators to establish patterns that can be investigated further. 

In fact, it is possible that this link is due to reverse causation. In other words, someone who is overweight or obese might be more inclined to consume ‘diet’ drinks to help with weight loss. 

In contrast, randomised controlled studies - considered the “gold standard” in scientific research - primarily report inclusion of artificial sweeteners in one's diet to have neutral effects (20) or even modest beneficial effects (21) on daily calorie intake and body weight. 

This may be especially true when sugar is replaced with artificial sweeteners (22).

For example, in one large 18-month long controlled study in 641 children aged 4-11, those drinking 250ml of an artificially sweetened  zero calorie drink in place of their usual sugary drink gained significantly less weight (~1kg) and body fat than those who continued to drink their sugary drink (21).

Taken together, the evidence suggests that artificial sweeteners may not cause weight gain but instead may be moderately effective for weight loss. 

Artificial Sweeteners and the Gut

Your gut bacteria plays a crucial role in your health. An imbalance of the gut bacteria (also known as gut dysbiosis) is associated with multiple health issues, such as weight gain (23), diabetes (24), and inflammatory bowel disease (25).

The composition and function of gut bacteria can differ from person to person and can be influenced by the things you eat, including certain artificial sweeteners (26). 

One study in humans reported that the artificial sweetener saccharin when consumed for one week caused an imbalance of healthy and unhealthy microbes in the guts of four of the seven participants (27).

As a result, the four participants classed as “responders” after only 5 days following consumption of the artificial sweetener showed worse blood sugar control (27).

In addition, when the gut bacteria from the affected human participants were transplanted into mice, the mice also showed worse blood sugar control (27).

Whereas, the blood sugar control of the mice transplanted with the gut bacteria of the “non-responders” was unaffected (27).

While an interesting finding, it’s important to note that this finding has only been reported in one study in humans, with a very small number of participants at that; and therefore larger human studies are needed before any conclusions can be made.

Artificial Sweeteners and Diabetes 

Opting for artificial sweeteners could be beneficial for those both with or without diabetes as they provide a sweet taste without the associated rise in blood sugar levels (28).

However, some long term studies have reported that drinking diet soft drinks is associated with a comparably higher risk of developing type 2 diabetes as drinking regular soft drinks (29, 30).

This may appear counterintuitive, but it’s important to remember that all of these studies were observational, and therefore did not necessarily show that diet soft drinks cause diabetes, but only that people who developed type 2 diabetes also consumed diet soft drinks. 

On the other hand, several controlled studies have shown that artificial sweeteners do not have an effect on blood glucose (sugar) or insulin levels mainly in healthy people, regardless of how they are consumed (14, 31, 32, 33, 34, 35, 36, 37).

To date, just one small study in non-hispanic black women has reported a negative effect.

When the participants consumed a drink made up of sucralose sweetened water versus just water before consuming 75g sugar, their peak blood sugar levels were 14% higher and their insulin levels 20% higher (38).

However, the participants in this study were obese, so might have a greater susceptibility to negative effects than those at a healthy weight. What’s more, individuals may possibly respond differently to artificial sweeteners depending on their racial or ethnic background. However, other studies that investigated predominantly non-hispanic white individuals found no effect (35, 36).

While the research findings are not in complete agreement, the current evidence largely supports the use of artificial sweeteners to avoid the effects that sugar has on blood sugar levels and insulin. 

Nevertheless, more research is needed to study their effects in different population groups, especially in those who are overweight or obese, and/or diabetic as these are indiviauls who will most likely already have related health complications. 

Conclusion

Overall, there appears to be no strong evidence from controlled studies to suggest that consuming artificial sweeteners has negative effects on appetite and bodyweight, and blood sugar control.

In fact, artificial sweetener consumption can even be an effective strategy for reducing calorie intake for weight loss, as well as controlling blood sugar, especially when used in place of sugar in your diet to reduce your added sugar intake. However, more long term research is needed to confirm this. 

If you normally use artificial sweeteners in moderation, and are healthy and satisfied with the results you are getting, it is not necessary to change anything.

 

References

  1. WHO, FAO & Commission CAC (2018) REPORT OF THE 50th SESSION OF THE CODEX COMMITTEE ON FOOD ADDITIVES [Internet]. Available from: <http://www.fao.org/fao-who codexalimentarius/shproxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FMeetings%252FCX-711-50%252FReport%252FREP18_FAe.pdf>.

  2. Swithers S. E. (2013) Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in endocrinology and metabolism: TEM, 24(9), pp.431–441. 

  3. Sylvetsky, A. C. & Dietz, W. H. (2014) Nutrient-content claims--guidance or cause for confusion?. The New England journal of medicine, 371(3), pp.195–198.

  4. 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), pp.35–47.

  5. Yarmolinsky, D.A., Zuker, C.S. and Ryba, N.J. (2009) Common sense about taste: from mammals to insects. Cell, 139(2), pp.234-244.

  6. Margolskee, R., Dyer, J., Kokrashvili, Z., Salmon, K., Ilegems, E., Daly, K., Maillet, E., Ninomiya, Y., Mosinger, B. & Shirazi-Beechey, S. (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proceedings of the National Academy of Sciences, 104 (38), pp.15075-15080.

  7. Kyriazis, G., Soundarapandian, M. & Tyrberg, B. (2012) Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proceedings of the National Academy of Sciences, 109 (8), pp.E524-E532.

  8.  US Food & Drug Administration (2018) Additional Information about High-Intensity Sweeteners [Internet]. Available from: <https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states>.

  9. Food Standards Agency (2019) Food additives [Internet]. Available from: <https://www.food.gov.uk/safety-hygiene/food-additives>.

  10. Swithers S. E. (2015) Artificial sweeteners are not the answer to childhood obesity. Appetite, 93, pp.85–90.

  11. Swithers S. E. (2013) Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in endocrinology and metabolism: TEM, 24(9), pp.431–441.

  12. 12. Frank, G., Oberndorfer, T., Simmons, A., Paulus, M., Fudge, J., Yang, T. & Kaye, W. (2008) Sucrose activates human taste pathways differently from artificial sweetener. NeuroImage, 39 (4), pp.1559-1569.

  13. Anton, S., Martin, C., Han, H., Coulon, S., Cefalu, W., Geiselman, P. & Williamson, D. (2010) Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite, 55 (1), pp.37-43.

  14. Maersk, M., Belza, A., Holst, J. J., Fenger-Grøn, M., Pedersen, S. B., Astrup, A. & Richelsen, B. (2012). Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. European journal of clinical nutrition, 66 (4), 523–529.

  15. Tate, D. F., Turner-McGrievy, G., Lyons, E., Stevens, J., Erickson, K., Polzien, K., Diamond, M., Wang, X. & Popkin, B. (2012) Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. The American journal of clinical nutrition, 95(3), pp.555–563.

  16. 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), pp.1415–1421.

  17. Rogers, P., Ferriday, D., Irani, B., Hei Hoi, J., England, C., Bajwa, K. & Gough, T. (2020) Sweet satiation: Acute effects of consumption of sweet drinks on appetite for and intake of sweet and non-sweet foods. Appetite, 149, pp.104631.

  18.  Azad, M. B., Abou-Setta, A. M., Chauhan, B. F., Rabbani, R., Lys, J., Copstein, L., Mann, A., Jeyaraman, M. M., Reid, A. E., Fiander, M., MacKay, D. S., McGavock, J., Wicklow, B. & Zarychanski, R. (2017) Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 189(28), pp.E929–E939.

  19. Fowler, S., Williams, K., Resendez, R., Hunt, K., Hazuda, H. & Stern, M. (2008) Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-term Weight Gain. Obesity, 16 (8), pp.1894-1900.

  20. Ebbeling, C. B., Feldman, H. A., Chomitz, V. R., Antonelli, T. A., Gortmaker, S. L., Osganian, S. K. & Ludwig, D. S. (2012) A randomized trial of sugar-sweetened beverages and adolescent body weight. The New England journal of medicine, 367(15), pp.1407–1416.

  21. de Ruyter, J. C., Olthof, M. R., Seidell, J. C. & Katan, M. B. (2012) A trial of sugar-free or sugar-sweetened beverages and body weight in children. The New England journal of medicine, 367(15), 1397–1406.

  22. 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), pp.381–394.

  23. . Zhang, H., Di Baise, J. K., Zuccolo, A., Kudrna, D., Braidotti, M., Yu, Y., Parameswaran, P., Crowell, M. D., Wing, R., Rittmann, B. E. & Krajmalnik-Brown, R. (2009) Human gut microbiota in obesity and after gastric bypass. Proceedings of the National Academy of Sciences of the United States of America, 106(7), pp. 2365–2370.

  24. 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., Lu, D., Wu, P. & Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), pp.55–60.

  25.  Frank, D. N., St Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N. & Pace, N. R. (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America, 104(34), pp.13780–13785.

  26. David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., Biddinger, S. B., Dutton, R. J. & Turnbaugh, P. J. (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), pp.559–563.

  27. 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), pp.181–186.

  28.  Gardner, C., Wylie-Rosett, J., Gidding, S., Steffen, L., Johnson, R., Reader, D. & Lichtenstein, A. (2012) Nonnutritive Sweeteners: Current Use and Health Perspectives: A Scientific Statement from the American Heart Association and the American Diabetes Association. Diabetes Care, 35 (8), pp.1798-1808.

  29. Imamura, F., O'Connor, L., Ye, Z., Mursu, J., Hayashino, Y., Bhupathiraju, S. N. & Forouhi, N. G. (2015) Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ (Clinical research ed.), 351, h3576.

  30. O'Connor, L., Imamura, F., Lentjes, M. A., Khaw, K. T., Wareham, N. J. & Forouhi, N. G. (2015) Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia, 58(7), pp.1474–1483.

  31. Ma, J., Bellon, M., Wishart, J., Young, R., Blackshaw, L., Jones, K., Horowitz, M. & Rayner, C. (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), pp.G735-G739.

  32. Ma, J., Chang, J., Checklin, H., Young, R., Jones, K., Horowitz, M. & Rayner, C. (2010) Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. British Journal of Nutrition, 104 (6), pp.803-806.

  33. Ford, H., Peters, V., Martin, N., Sleeth, M., Ghatei, M., Frost, G. & Bloom, S. (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), pp.508-513.

  34. Steinert, R., Gerspach, A., Gutmann, H., Asarian, L., Drewe, J. & Beglinger, C. (2011) The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clinical Nutrition, 30 (4), pp.524-532.

  35. Brown, R., Walter, M. & Rother, K. (2011) Effects of Diet Soda on Gut Hormones in Youths With Diabetes. Diabetes Care, 35 (5), pp.959-964.

  36. Brown, A., Bohan Brown, M., Onken, K. & Beitz, D. (2011) Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women. Nutrition Research, 31 (12), pp.882-888.

  37. Goza, R., Bunout, D., Barrera, G., de la Maza, M. P. & Hirsch, S. (2018) Effect of Acute Consumption of Artificially Sweetened Beverages on Blood Glucose and Insulin in Healthy Subjects. Journal of Nutrition & Food Sciences, 08 (04).

  38. Pepino, M., Tiemann, C., Patterson, B., Wice, B. & Klein, S. (2013) Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load. Diabetes Care, 36 (9), pp.2530-2535.

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