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Might sucralose promote energy imbalance?

Sucralose, commonly sold as Splenda™, has had a ton of safety research done on it. But there's a mechanism by which it could theoretically promote weight gain.

Study under review: Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response


Synthetic sweeteners are found in thousands of food and drink products and are consumed by millions of people on a daily basis. Despite being mostly calorie-free and lacking any nutritive quality, their impact on human metabolic health remains uncertain. Some scientists have concluded that synthetic sweeteners may contribute to metabolic dysregulation[1] whereas others suggest there is no valid association[2].

Synthetic sweeteners are artificial sugar substitutes that are designed to limit energy intake[3], have zero effect on blood sugar[4] levels, and improve dental health[5] by reducing dental plaque formation. Sweeteners approved for human consumption include acesulfame potassium, aspartame, saccharin, and sucralose, and are between 200 to 600[6] times sweeter than sugar (see Figure 1 for specific levels). Most sweeteners are usually sold as mixtures with carbohydrates, such as dextrose and maltodextrin, and so aren’t technically calorie free.

Many people replace sugar with sweeteners in order to assist in weight loss and help regulate blood sugar levels. Individuals with type 2 diabetes[7] have high blood sugar issues, with insulin resistance in peripheral tissues. Therefore, as a sugar substitute, sweeteners may in theory allow individuals to still eat sweet foods without compromise.

But there may be a downside when the brain gets signals that sweets are being eaten but fewer calories are consumed. Within the brain there are established satiety[8] and hunger[9] networks that are involved in the regulation of energy homeostasis. These networks are closely associated with energy sensors such as AMP kinase (AMPK) and confer control over appetite[10] and food intake[11]. AMPK[12] also plays a major role in regulating insulin synthesis and secretion. Insulin[13] regulates the peripheral energy and glucose metabolism in the body by processes like making cells in the liver and muscle take up glucose from the blood for storage as glycogen. However, there are also insulin receptors in the brain[14], where it could influence feeding behavior[15].

Figure 1: Sweetness of common synthetic sweeteners relative to sucrose

Reference: Bellise et al. Eur J Clin Nutr. 2007 Jun.

Some researchers have suggested that artificial sweeteners can affect these neuronal pathways and may cause an energy imbalance that actually promotes hunger and increases appetite. Observational studies would appear to support this, suggesting that synthetic sweetener consumption is associated with metabolic disease across all age groups: children[16], adults[17], and the elderly[18].

In addition, some human studies have shown that synthetic sweeteners can enhance appetite[19] and promote hunger[20], suggesting that it is the increase in food consumption that causes the metabolic dysregulation in sweetener users. Although there is still much debate, a recently published study sought to clarify the effect of sucralose on appetite and food intake, using a fly model.

Non-nutritive sweeteners are consumed by millions of people on a daily basis. However, the relationship between their consumption and metabolic disorders is unclear. By disassociating sweetness from calories, there may be a mechanism linking non-nutritive synthetic sweeteners to increased weight gain.

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