Understanding the metabolic and health effects of low-calorie sweeteners: methodological considerations and implications for future research

Sylvetsky, Allison C.; Blau, Jenny; Rother, Kristina I.

doi:10.1007/s11154-016-9344-5

Cited by 36 publications

(35 citation statements)

References 70 publications

(109 reference statements)

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“…Although artificial sweeteners are marketed as healthy alternatives for consumers seeking to avoid sugar-containing products (de la Pena 2010), several studies have shown a positive correlation between weight gain and consumption of such products (Stellman and Garfinkel 1988; Fowler et al 2008). However, the effects of artificial sweeteners remain controversial as results appear to be somewhat dependent on experimental conditions (Sylvetsky et al 2016). …”

Section: Discussionmentioning

confidence: 99%

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Gul

Hamilton

Munoz

et al. 2017

Appl. Physiol. Nutr. Metab.

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Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Gul

Hamilton

Munoz

et al. 2017

Appl. Physiol. Nutr. Metab.

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“…68 All were relatively short in duration, and the majority were conducted as part of multifaceted weight loss programs in obese individuals, which does not address routine consumption of nonnutritive sweeteners by healthy individuals. In addition, some trials evaluated nonnutritive sweeteners in capsule form, which may alter their physiologic effects, while others were subject to potential bias from lack of blinding and industry sponsorship.…”

Section: Limitationsmentioning

confidence: 99%

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies

Azad

Abou‐Setta

Chauhan

et al. 2017

CMAJ

284

223

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“…Given the ongoing controversy surrounding the role of LCSs in weight management and chronic disease, we recently highlighted several key methodologic issues (4), including the need to correctly categorize LCS exposure of clinical study volunteers and to take this information into account when interpreting study findings. Recent data show that w25% of children and 40% of adults in the United States consume foods, beverages, or packets [e.g., Splenda (Heartland Consumer Products) or Equal (Merisant Company), often added to tea and coffee as sugar substitutes] containing LCSs (5).…”

Section: Introductionmentioning

confidence: 99%

Widespread sucralose exposure in a randomized clinical trial in healthy young adults

Sylvetsky

Walter²,

Garraffo³

et al. 2017

The American Journal of Clinical Nutrition

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Background: Low-calorie sweeteners (LCSs) are found in many foods and beverages, but consumers may not realize their presence, and their role in appetite, weight, and health is controversial. Although consumption limits based on toxicologic safety are well established, the threshold required to exert clinically relevant metabolic effects is unknown. Objectives: This study aimed to determine whether individuals who do not report consumption of LCSs can be correctly characterized as "unexposed" and to investigate whether instructions to avoid LCSs are effective in minimizing exposure. Design: Eighteen healthy 18-to 35-y-old "nonconsumers" (,1 food or beverage with LCSs/mo) enrolled in a 2-wk trial designed to evaluate the effects of LCSs on the gut microbiota. The trial consisted of 3 visits. At baseline, participants were counseled extensively about avoiding LCSs. After the run-in, participants were randomly assigned to consume diet soda containing sucralose or carbonated water (control) 3 times/d for 1 wk. Food diaries were maintained throughout the study, and a spot urine sample was collected at each visit. Results: At baseline, 8 participants had sucralose in their urine (29.9-239.0 ng/mL; mean 6 SD: 111.4 6 91.5 ng/mL). After the run-in, sucralose was found in 8 individuals (2 of whom did not have detectable sucralose at baseline) and ranged from 25.0 to 1062.0 ng/mL (mean 6 SD: 191.7 6 354.2 ng/mL). Only 1 participant reported consumption of an LCS-containing food before her visit. After the intervention, sucralose was detected in 3 individuals randomly assigned to receive carbonated water (26-121 ng/mL; mean 6 SD: 60.7 6 52.4 ng/mL). Conclusions: Despite the selection of healthy volunteers with minimal reported LCS consumption, more than one-third were exposed to sucralose at baseline and/or before randomization, and nearly half were exposed after assignment to the control. This shows that instructions to avoid LCSs are not effective and that nondietary sources (e.g., personal care products) may be important contributors to overall exposure. This trial was registered at clinicaltrials.gov as NCT02877186.Am J Clin Nutr 2017;105:820-3.

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Understanding the metabolic and health effects of low-calorie sweeteners: methodological considerations and implications for future research

Cited by 36 publications

References 70 publications

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies

Widespread sucralose exposure in a randomized clinical trial in healthy young adults

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