Non-nutritive Sweeteners and Their Associations with Obesity and Type 2 Diabetes

Walbolt, Jarrett, and Yunsuk Koh.

Jun 30, 2020

Journal of Obesity and Metabolic Syndrome. 2020;29(2):114-123.

Evidence linking the excessive consumption of nutritive sweeteners (NS) to adverse metabolic health outcomes has led to an increase in consumption of non-nutritive sweeteners (NNS), particularly among the obese and individuals with diabetes. NNS are characterized by having zero-to-negligible caloric load, while also having a sweet taste. They are utilized as a replacement for traditional NS to reduce energy intake and to limit carbohydrate-related negative health outcomes. However, recent studies have suggested that NNS may actually contribute to the development or worsening of metabolic diseases, including metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease. Thus, it is imperative to understand the NNS efficacy and the relationship between NNS and metabolic diseases.

Non-nutritive sweeteners (NNS) were first introduced as early as 1878 as replacements for standard table sugar. NNS are characterized by providing few to no calories, whereas nutritive sweeteners (NS), such as standard table sugar, contain a caloric load. Both NNS and NS contribute to the flavor and texture of foods, primarily sweet taste. NNS are, however, significantly sweeter than NS, by as many thousands of times. Due to their extraordinary sweetness, much less of the substance is added to foods by consumers, thus reducing caloric intake. Obese and diabetic individuals use NNS to reduce caloric and carbohydrate intake for weight management, as well as for glycemic control. NNS are derived from either chemical or natural sources. For instance, aspartame, acesulfame potassium, and sucralose are derived from chemical sources, while stevia and its extract stevioside come from natural sources.

The global market for NNS grew 5.1% annually between 2008 and 2015. Consumption of NNS sweetened beverages by American adults increased from 21.1% in 2003–2004 to 24.9% in 2009–2010. In Korea, while NNS consumption is well below acceptable daily intake levels, there is some evidence to suggest that there may be a trend towards reduced intake in recent years. Commercial NNS that have been approved by the United States Food and Drug Administration are listed in Table 1. During the same time span, consumption by children jumped from 7.8% to 18.9%. NNS consumption has become increasingly popular among women and children in particular. The exact reasons that NNS use has grown in these demographics is unknown, although speculations can be made. Women are more likely to attempt weight loss, and are therefore likely to selectively choose products labeled as “no sugar,” “diet,” or “reduced sugar” that contain NNS instead of standard table sugar (sucrose). While NNS-sweetened beverage consumption has increased in adults regardless of degree of adiposity, only normal weight children showed increases.

Obesity is linked to many adverse health outcomes, including higher risks of developing diabetes and cardiovascular disease. Obesity is no longer only a concern in Western countries, but in Asian countries as well. The Korean Society for the Study of Obesity reports a steadily increasing rate of obesity, from 29.7% in 2009 to 32.4% in 2015. The associated national health care expenditure is $1.8 billion. While sucrose does not directly cause diabetes, it has been linked to negative impacts on glucose tolerance in healthy individuals. Diets high in sucrose have also been shown to cause weight gain and obesity, which can lead to the development of diabetes. Large visceral fat stores cause fat cells to release proinflammatory cytokines. This puts the body into an inflammatory state, which can make insulin responsive cells insensitive to the presence of insulin. Compounding the insensitivity brought on by inflammation, adipose tissue may release fat molecules into the blood, which may in turn lead to additional reduced insulin sensitivity.

Diabetes mellitus is a chronic metabolic disease that disrupts the hormonal networks responsible for stabilizing blood glucose levels through the absolute or relative hindrance of insulin secretion and/ or deficits in insulin resistance. Diabetes is a growing worldwide epidemic. In the United States alone, 30.3 million individuals, or 9.4% of the population, have diabetes. Furthermore, a staggering 84.1 million Americans have prediabetes, placing them at immediate risk of developing diabetes. Type 2 diabetes is characterized by a combination of β-cell dysfunction and a resistance to insulin that is released. Diabetes represents a significant financial burden on healthcare systems, as it accounts for more than 10% of total healthcare spending in the United States, Canada, and Europe. This burden is likely to increase even more in the coming years.

Research has brought the efficacy of using NNS to ameliorate or prevent metabolic diseases into scrutiny. Despite widespread usage, their supposed benefits have yet to be verified. In fact, some evidence suggests that NNS are associated with metabolic disease, particularly obesity. Since NNS have zero to very minor caloric load, they cannot contribute directly to obesity, but instead may influence metabolic processes. Research has uncovered multiple mechanisms that may play roles in how NNS could trigger metabolic disease.

Researchers have yet to fully describe the long-term or acute effects of NNS consumption on metabolic diseases. Currently, the results of many studies appear contradictory, although this may be due to flaws in the two most commonly utilized study designs. Randomized, crossover designs are ideal for controlled studies, but fail to account for long term effects and human behavior in free-living scenarios. Conversely, prospective cohort studies show that NNS users are more likely to have metabolic disease but are biased, since individuals with metabolic disease are more likely to consume NNS in the first place. There is a need for research designed to combat these specific flaws.

More studies are also needed to provide insights into the mechanisms by which NNS may affect metabolic health, both positively and negatively. Research has yet to determine the effects of chronic NNS consumption, to see whether NNS act as a beneficial tool to combat overconsumption of carbohydrates or if NNS pose equal or greater risks as a NS.

Full Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338497/

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