No Free Lunch: the Story of Non-Caloric Artificial Sweetners

Non-caloric artificial sweeteners (NAS) are sugar substitutes used to give sweetness to food and drinks without the inconvenient calories; to those among us with a sweet tooth their unique properties may seem too good to be true. NAS are widely used in processed foods, soft drinks, and diet products.  In the United States, the most commonly used NAS compounds are saccharin (e.g. Sweet N’Low), aspartame (e.g. Nutrasweet), and sucralose (e.g. Splenda), all of which have been approved by the Federal Drug Administration (FDA) which regulates the use of NAS as food additives.  The FDA has also approved three other NAS food additives (neotame, advantame, and acesulfram potassium) and had ‘no objection’ to the use of Stevia, a plant-based sweetener, in foods because it is generally regarded as safe.  Despite the long history of NAS consumption (Stevia has been used as a sweetener for centuries in South America and saccharin was first synthetized in 1879) and the FDA evaluation and approval of specific NAS, there has been a lingering suspicion that their unique properties may indeed be too good to be true.  A scientific paper (1) published in the journal Nature in late 2014 provides indirect evidence that the widespread use of NAS is not good for human health and supports those who are skeptical of the concept of a free lunch.

The authors examined the effect of adding formulations of each of three common NAS (saccharin, sucralose, aspartame) to the diet of mice. The main findings were that the NAS led to abnormal glucose tolerance* in the mice and this was associated with specific changes in the gut flora (microbiota) of these mice. Transfer of the gut flora from the treated to a group of untreated mice (by fecal transplant) led to the development of glucose intolerance in the recipients indicating that the change in the composition of the micobiota led to the abnormal glucose metabolism.  The authors also studied the association between NAS consumption and physical and metabolic measurements in 381 human subjects and found that there was a positive correlation between the amount of NAS they consumed and increases in body weight and blood glucose and in the prevalence of abnormal glucose tolerance.  Finally, they supplemented the diet of seven healthy human volunteers with the maximum acceptable daily dose of NAS recommended by the FDA for a period of seven days and found that four out of seven developed abnormal glucose metabolism in this short period of time.  Although none of the findings in the study provide definitive proof that the regular consumption of NAS in food is an important contributor to the explosion in the prevalence of diabetes and obesity in the economically advantaged parts of the world, the data should give those who regularly reach for a diet soda a moment of pause.

(1) Suez J et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.  Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793.

*The glucose tolerance test is a method used to assess how the body metabolizes a standard infusion of glucose over a two-hour period. First, the baseline fasting blood glucose is measured then another blood glucose level if measured two hours after the ingestion of a specific amount of glucose (in humans for example, the standard dose of glucose used for the test is 75 gm).  The principle on which the test is based is that normal metabolism tightly regulates the increase in blood glucose through the release of insulin which shifts the glucose from the blood stream into the tissues.  Therefore, one can predict the blood glucose two hours after being given a specific amount of glucose and departures from that prediction indicate abnormal glucose tolerance.  For example, in human subjects the blood glucose two hours after ingestion of 75 gm glucose should be less than 140 mg/dL; levels between 140 and 199 mg/dL indicate abnormal glucose tolerance, and levels greater than 199 mg/dL are diagnostic of diabetes.