The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements.

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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.

Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides.

Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation.

Diet soft drink consumption is associated with an increased risk of vascular events in the Northern Manhattan Study.

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.

Dietary intake and the development of the metabolic syndrome: the Atherosclerosis Risk in Communities study.

Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community.

The Australian paradox: a substantial decline in sugars intake over the same timeframe that overweight and obesity have increased.

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.

Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association.

Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners.

Glossary

also known as ‘diet’ soft drinks, beverages manufactured with one or more high-intensity sweeteners in place of energy-yielding sugars like sucrose or high-fructose corn syrup with the purpose of reducing or eliminating calories.

used as an index of risk for weight-related health outcomes and is calculated as (kg/m2). In adults BMIs of 18.5–24.9 are considered to be within the normal range, whereas BMIs from 25 to 29.9 are classified as overweight and a BMI greater than 30 is classified as obese.

statistical measures of how often an event occurs in one group compared to another. A HR or OR of 1 means there is no difference between the groups and an HR or OR >1 means there is an increased likelihood that the event will occur in the group of interest relative to the comparison group.

also known as low-calorie sweeteners, artificial sweeteners, non-nutritive sweeteners, or noncaloric sweeteners are chemicals that produce the perception of sweet taste at very low concentrations. High-intensity sweeteners currently used commonly in foods and beverages include sucralose, aspartame, saccharin, and acesulfame potassium, as well as newly approved extracts from the plant Stevia rebaudiana. Although some high-intensity sweeteners can be metabolized by the body, foods and beverages typically contain them in such small quantities that even those that can be metabolized contribute minute amounts of energy to the diet.

hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) that are released from L cells and K cells in the intestine, respectively, and serve to enhance the release of insulin from beta cells, slow the rate of gastric emptying, and may contribute to satiety.

a group of factors that occur together and contribute to increased risk for coronary artery disease, stroke, and type 2 diabetes (T2D). Typical definitions require three or more of the following: blood pressure >130/85 mmHg; fasting blood glucose >100 mg/dl; large waist circumference (men >102 cm, women >89 cm); low high-density lipoprotein (HDL) cholesterol (men <40 mg/dl; women <50 mg/dl); triglycerides >150 mg/dl.

following meals (post-prandial) levels of glucose in the blood are tightly regulated by the release of a variety of hormones that contribute to clearance of glucose. For example, release of insulin from the beta cells of the pancreas is required to move sugar from the blood into cells.

also known as ‘regular’ soft drinks, manufactured with one or more caloric sweeteners such as sucrose or high-fructose corn syrup.

increase in metabolic rate after consumption of a meal related to energy required to process and metabolize the consumed food.

chronic elevation of blood glucose due to insulin resistance that is also characterized by impaired incretin secretion.