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Non-sugar sweeteners (NSS) and obesity

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Non-nutritive sweeteners (NNS) and glycaemia

Non-nutritive sweeteners (NNS) (artificial sweeteners) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses (1)

  • NNS do not contain calories and are thereby presumed to be inert and not elicit a postprandial glycemic response (1)
  • human gastrointestinal tract harbors trillions of microorganisms that play critical roles in multiple aspects of human physiology and pathologies, including cardiometabolic health (1)
    • the assemblage of microorganisms varies between individuals (and between animals in different research vivaria), leading to personalized responses to diets
  • Suez et al causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement.
    • by performing extensive fecal transplantation of human microbiomes into germ-free (GF) mice, demonstrated a causal and individualized link between NNS-altered microbiomes and glucose intolerance developing in non-NNS-consuming recipient mice
    • groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses
    • study authors concluded that human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications
      • noted that the impacts on the microbiome are causally linked to elevated glycemic response
      • "...our study suggests that commonly consumed NNS may not be physiologically inert in humans as previously contemplated, with some of their effects mediated indirectly through impacts exerted on distinct configurations of the human microbiome. We stress that these results should not be interpreted as calling for consumption of sugar, which is strongly linked to cardiometabolic diseases and other adverse health effects.."

NNS (artificial sweeteners) and risk of cardiovascular disease (2)

  • in this large scale, prospective cohort of French adults, artificial sweeteners (especially aspartame, acesulfame potassium, and sucralose) were associated with increased risk of cardiovascular, cerebrovascular, and coronary heart diseases
  • results suggest that artificial sweeteners might represent a modifiable risk factor for cardiovascular disease prevention
  • findings indicate that these food additives, consumed daily by millions of people and present in thousands of foods and beverages, should not be considered a healthy and safe alternative to sugar, in line with the current position of several health agencies

AWorld Health Organization (WHO) systematic review of a large number of RCTs, prospective cohort studies and case-control studies found that (3)

  • non-sugar sweeteners (NSS) use results in a small reduction in body weight and BMI in adults, as assessed in RCTs (low certainty evidence) without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids and blood pressure (very low to high certainty evidence)
    • effects appear more pronounced when NSS are compared with sugars, and it is likely that they are mediated by a reduction in energy intake, which is only
      observed in studies in which NSS are compared to sugars
      • when NSS are used specifically as replacements for sugars (mostly in the form of replacing SSBs (sugar-sweetened beverages) with NSS-sweetened beverages), the effects on body weight and BMI are smaller, and neither are statistically significant (moderate certainty evidence)

    • results from prospective cohort studies suggest that higher NSS intake is associated with increased body weight, and increased risk of type 2 diabetes, cardiovascular diseases and all cause mortality (very low to low certainty evidence)

    • results from case-control studies suggest an association between saccharin intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies (very low to low certainty evidence)

    • results for pregnant women suggest that higher NSS intake is associated with increased risk of preterm birth (low certainty evidence) and possibly adiposity in offspring (very low certainty evidence)


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