Are Low-Cal Sweeteners at the End of Their Game?

Evidence-Based Diabetes Management, December 2014, Volume 20, Issue SP18

Advertisements are full of claims for sweeteners being “natural” or “no-calorie” replacements for sugars that can help support a healthy lifestyle. These products would seem to be ideal alternatives for a person with hyperglycemia: a sweetener minus the carbohydrates and the accompanying calories. But promotions don’t tell the full story, as a study by Suez et al, published in the journal Nature, discovered. Some of these noncaloric artificial sweeteners (NAS) can alter the intestinal microbiome, leading to glucose intolerance.1

What Has the FDA Approved?

Thus far, 6 artificial sweeteners have been sanctioned by the FDA (see Table): acesulfame potassium, aspartame, saccharin, sucralose, neotame,2 and most recently, advantame.3 Because they are not metabolized by the body, they do not add calories to a drink or food item. However, the additives in these products can add to their calorie and sugar content.2

Health Effects of Artificial Sweeteners

In the study by Suez et al, the authors, most of whom are at the Weizmann Institute of Science in Israel, fed an NAS supplement (saccharin, sucralose, or aspartame) to mice, and observed a significant increase in their blood glucose levels compared with the control mice, which consumed sugar.4 This pattern was observed in mice fed a normal diet as well as in those fed a high-fat diet (obesity model). The role of the gut flora in regulating blood sugar levels was then confirmed by 2 separate experiments:

• treatment with antibiotics purged NAS-induced glucose intolerance, in both diet groups;

• transplanting feces from NAS-fed mice to germ-free mice changed the composition of their gut microbial flora and elevated their blood glucose levels as well.4

Using the paradigm of the mouse model, the authors replicated their experiments in 400 human subjects and discovered differences in the patterns of microbial flora expressed in the gut of NAS consumers, along with an increase in their blood sugar levels. A high-NAS diet in 7 trial participants confirmed the hypothesis: just 4 days into a 7-day experimental period, 50% of participants possessed altered bacterial composition and elevated blood glucose levels.

Thus, this study by Suez et al confirmed that the same artificial sweeteners that are advertised to overweight consumers as a tool to help them lose weight may actually contribute to or worsen the condition of individuals with metabolic abnormalities, such as diabetes and obesity.4

Taking this a step further, David L. Katz, MD, MPH, FACPM, FACP, director, Yale University Prevention Research Center, wrote in an article, “Is it possible that chemicals in our food, to which we of course have no native adaptations, are contributing to some or all of the subtle but indirect harms? The precautionary principle argues that we don’t assume something is entirely safe just because we don’t have proof that it’s dangerous. These are chemical compounds, not food, and we know our native diet was made up of food.”5

Old Story, New Headline

These results are not at all a surprise. Back in 2008, researchers fed the sweetener Splenda—composed of sucralose, maltodextrin, and glucose—to rats for 12 weeks, and analyzed their gut microbes as well as expression of 2 enzymes: a membrane efflux transporter, P-glycoprotein, and a metabolizing enzyme, cytochrome P-450. The 2 enzymes play an important role in restricting the bioavailability of oral drugs. Along with changes in the microbial composition, Splenda increased the expression of both enzymes at the end of the 12-week period.6 (Note: the changes noted were at FDA-approved levels of sucralose.)

The debate on the health effects of one of the earliest NASs, aspartame, lingers today. While the Nature paper drew attention to the metabolic effects of aspartame, this popular NAS has previously been shown to be a cause of cancer,7 developmental deficits, and neuronal toxicity.8

More Common Now Than Before

Bread, cereal, soda, canned products, jams and jellies, fruit spreads, dried fruits, chewing gum, candy, dairy-based drinks and desserts, sauces, soups and broths, flavored drinks…name the product, and it’s easy to find an artificial sweetener in the ingredients.9 Despite all the evidence on the health effects of NAS, their use has not dwindled.

Between 1999 and 2004, a significant increase in the number (more than 6000) of food products claiming to be noncaloric—containing artificial sweeteners—was noted. According to the National Household Nutritional Survey, as of 2004, about 15% of the population in the United States regularly used artificial sweeteners.10 The addiction of the population to diet drinks is highlighted by a data brief released by the CDC’s National Center for Health Statistics. Between 2009 and 2010, 20% of the population in the United States 2 years and older consumed diet drinks (see Figure 1).11 Many individuals with diabetes commonly use artificial sweeteners as an alternative to sucrose.12 With the high incidence of diabetes—29.1 million people, or 9.3% of the population, as of 2012—an increased vigilance on the impact of these sweeteners is essential.

The obesity epidemic in the United States, which has affected one-third of the adult population,13 points to sugar and other caloric sweeteners as the primary culprits,10 and has led to an increase in the utilization of weight loss products, including sweeteners.14 Often, individuals who are weight conscious consider artificial sweeteners “healthy,” despite several large studies indicating the opposite. Preload experiments have found that human appetite is enhanced by sweet taste, whether it be from sugar or artificial sweeteners, while studies in rats identified an increased weight gain along with an elevated total energy intake when supplemented with saccharin compared with glucose.10

Global Market Access

A research report evaluating market penetration of sweeteners, published by Mintel and Leatherhead Food Research, has reported that stevia, the natural, plant-based

sweetener, is gaining a lot of traction with consumers and nudging more established sweeteners, like aspartame, from their pedestal. Stevia was valued at $110 million in 2013—based on its global use in the food and beverage industry—a number expected to escalate by 2.5-fold by the year 2017 to $275 million. Aspartame, which held a market share of $437 million in 2013, is likely to plummet to $328 million by 2017, as stevia and acesulfame K grow more popular.15

The numbers estimated in the report underscore the popularity of these intense artificial sweeteners in the food and beverage industry. A 2.8% increase from 2012 to 2013, saw the global sweetener market reach $1.27 billion, and it is predicted to reach $1.4 billion by 2017, an almost 10% spike.15

Wrote Katz in his blog on LinkedIn, “Neither the current excess of sugars, nor the sugar substitutes that foster a sweet tooth and disrupt the microbiome,” is an answer to our problem. “There may be better options in the pipeline, namely non-caloric sweeteners that don’t exert unintended harms. Both stevia and monk fruit extract look promising at this point, but we need more data.”16


If these estimates are to be believed, they imply that the use of artificial sweeteners is on the rise, despite all the controversial research reports on their health outcomes. But then, you have people who believe sugar is a carcinogen. So it just depends on where your interests lie! References

1. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-186.

2. Low-calorie sweeteners. American Diabetes Association website. Reviewed August 1, 2013. Accessed September 12, 2015.

3. How sweet it is: all about sugar substitutes. FDA website. Published May 19, 2014. Accessed November 12, 2014.

4. Feehley T, Nagler CR. Health: the weighty costs of non-caloric sweeteners. Nature. 2014;514(7521):176-177.

5. Katz DL. Too sweet for the sweet spot. U.S. News & World Report website. Published August 5, 2013. Accessed November 21, 2014.

6. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-1429.

7. Soffritti M1, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect. 2007;115(9):1293-1297.

8. Lau K, McLean WG, Williams DP, Howard CV. Synergistic interactions between commonly used food additives in a developmental neurotoxicity test. Toxicol Sci. 2006;90(1):178-187.

9. Myers W. Complete list of artificial sweeteners. Liveto110 website. Published May 19, 2013. Accessed November 12, 2014.

10. Yang Q. Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med. 2010;83(2):101-108.

11. Fakhouri THI, Kit BK, Ogden CL. Consumption of diet drinks in the United States, 2009-2010. NCHS Data Brief. 2012;109:1-8.

12. Colagiuri S, Miller JJ, Edwards RA. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus. Am J Clin Nutr. 1989;50(3):474-478.

13. Overweight and Obesity. CDC website. http:// Reviewed September 9, 2014. Accessed October 29, 2014.

14. Hill SE, Prokosch ML, Morin A, Rodeheffer CD. The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction. Appetite. 2014;83C:82-88.

15. Stevia set to steal intense sweetener market share by 2017, reports Mintel and Leatherhead Food Research. Mintel website. Published January 14, 2014. Accessed November 12, 2014.

16. Katz DL. Seeking the sweet spot, from mouth to microbiome. LinkedIn website. Published September 23, 2014. Accessed November 21, 2014.