Why sucralose diet drinks and sugar drinks differ

This topic might be considered by some as slightly obtuse to the theme of gene-environment interactions; but the environmental signal is “diet drinks, with vs without nonsweetened carbohydrate,” and there is variability in alleles of genes in each of our genomes that respond to this signal. There is substantial controversy about effects of drinking excessive amounts of zero- or low-calorie sweeteners (LCSs). Clinical studies have noted that LCS consumption is associated with increased risk of weight gain and/or diabetes, or with lower body mass index (BMI) and weight loss, or unrelated to metabolic and body weight measures. Similar inconsistencies exist in animal studies.

Central to resolving this debate is defining and testing biologically plausible mechanisms by which LCSs could lead to metabolic perturbation. Among suggested mechanisms: [a] LCS binding to extra-oral taste receptors in pancreas and intestine might influence glucose absorption by affecting glucose transporters SGLT1 and GLUT2 or by altering glucose metabolism by promoting incretin release that stimulate decreases in blood glucose levels [there are three intestinal glucose transporters — sodium/glucose co-transporters-1 (SGLT1) and -2 (SGLT2), and facilitative glucose transporter-2 (GLUT2) — in intestinal mucosal cells]; [b] central nervous system (CNS)-sensing of sweetness-elicited conditioned responses, leading to the subsequent development of glucose intolerance.

Authors [see attached article] randomly assigned 45 healthy volunteers to consume [a] beverages sweetened with sucralose

(sweet uncoupled from calories – LCS), [b] beverages sweetened with sucrose (sweet coupled with calories – Sugar), or [c] beverages sweetened with sucralose combined with maltodextrin (Combo). Oral glucose tolerance tests, sensory tests, and neuroimaging were conducted before and after participants consumed seven of their assigned beverages over 2 weeks in the laboratory.

Sucralose over 10 days is known to decrease insulin sensitivity in healthy human participants — an effect that correlates

with reductions in midbrain, insular, and cingulate responses to sweet (but not sour, salty, or savory) taste, as assessed by functional magnetic resonance imaging (fMRI). Authors found that taste perception was unchanged; i.e. consuming the carbohydrate (sucrose or sucralose) alone had no effect. However, consumption of sucralose in the presence of a “non-sweet carbohydrate” (maltodextrin) rapidly impairs glucose metabolism, resulting in longer-term decreases in brain, but not “perceptual sensitivity to sweet taste.” These findings (not surprisingly?) suggest “dysregulation of gut-brain control of glucose metabolism,” i.e. the brain receives these mixed signals and then responds by perturbing glucose metabolism. ☹


Cell Metab 2020; 31: 493-502

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