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Cited by 358Biochemical Analysis and Sensing TechniquesDiet, Metabolism, and DiseaseRegulation of Appetite and Obesity

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Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies

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Rogers, P J, Hogenkamp, P S, de Graaf, C, Higgs, S, Lluch, A, Ness, A R, Penfold, C, Perry, R, Putz, P, Yeomans, M R, Mela, D J·2016·International Journal of Obesity
DOI 10.1038/ijo.2015.177PMC PMC4786736
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Abstract

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-)(2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to -0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.

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Figure 1 Flow of information through the different phases of the systematic review.
Figure 1 Flow of information through the different phases of the systematic review.CC BY · PubMed Central
Figure 2 Forest plot showing individual and combined effect sizes for prospective cohort studies reporting the association between LES consumption and change in BMI over the follow-up period. Effect sizes have been standardised to a 1 year follow-up period. Negative scores favour LES consumption (BMI decrease). Squares represent change in BMI per year for the individual studies; square size is proportional to the weight of each study; horizontal lines represent 95% CIs. Diamonds represent the summary estimates and 95% CIs from random effects models for associations in adults and children separately, and in adults and children combined. BMI, Body Mass Index; LES, low-energy sweetener.
Figure 2 Forest plot showing individual and combined effect sizes for prospective cohort studies reporting the association between LES consumption and change in BMI over the follow-up period. Effect sizes have been standardised to a 1 year follow-up period. Negative scores favour LES consumption (BMI decrease). Squares represent change in BMI per year for the individual studies; square size is proportional to the weight of each study; horizontal lines represent 95% CIs. Diamonds represent the summary estimates and 95% CIs from random effects models for associations in adults and children separately, and in adults and children combined. BMI, Body Mass Index; LES, low-energy sweetener.CC BY · PubMed Central
Figure 3 Summary of outcomes of meta-analyses of short-term intervention studies comparing the effects on EI of LES versus sugar (for adults and children separately and combined), LES versus unsweetened products, LES versus water, LES versus nothing and LES in capsules versus placebo capsules. EI difference is the difference in cumulative EI (total of preload plus test meal EI) for the LES condition minus the comparison condition. Negative scores favour LES (that is, lower cumulative intake with LES). Filled diamonds represent the summary estimates and associated 95% CIs from random effects models of all studies included in the comparison. Unfilled diamonds represent the summary random effects estimates and 95% CIs for studies of adults and children separately. Many of the included studies reported multiple results for the same participants within the same comparison (for example, LES versus several different sugars). Treating these multiple results as independent potentially biases estimates of the variance of the summary effect sizes (see Supplementary Information methods section). Therefore, only the first set of results reported from each study was analysed. Accordingly, the total number of comparisons analysed (129) is less than the total recorded (218). EI, energy intake; LES, low-energy sweetener.
Figure 3 Summary of outcomes of meta-analyses of short-term intervention studies comparing the effects on EI of LES versus sugar (for adults and children separately and combined), LES versus unsweetened products, LES versus water, LES versus nothing and LES in capsules versus placebo capsules. EI difference is the difference in cumulative EI (total of preload plus test meal EI) for the LES condition minus the comparison condition. Negative scores favour LES (that is, lower cumulative intake with LES). Filled diamonds represent the summary estimates and associated 95% CIs from random effects models of all studies included in the comparison. Unfilled diamonds represent the summary random effects estimates and 95% CIs for studies of adults and children separately. Many of the included studies reported multiple results for the same participants within the same comparison (for example, LES versus several different sugars). Treating these multiple results as independent potentially biases estimates of the variance of the summary effect sizes (see Supplementary Information methods section). Therefore, only the first set of results reported from each study was analysed. Accordingly, the total number of comparisons analysed (129) is less than the total recorded (218). EI, energy intake; LES, low-energy sweetener.CC BY · PubMed Central
Figure 4 Forest plots showing individual and combined effect sizes for sustained intervention studies comparing the effects on BW of LES versus sugar (upper panel) and LES versus water (lower panel). Mean difference is weight change (end point minus baseline) in the LES condition minus weight change in the sugar condition over the intervention period (a negative score favours LES). Squares represent mean difference in BW for the individual comparisons; square size is proportional to the weight of each comparison; horizontal lines represent 95% CIs; diamonds represent the summary estimates and 95% CIs from random effects models for comparisons in adults for LES versus sugar, adults and children for LES versus sugar, and adults for LES versus water. BW, body weight; LES, low-energy sweetener.
Figure 4 Forest plots showing individual and combined effect sizes for sustained intervention studies comparing the effects on BW of LES versus sugar (upper panel) and LES versus water (lower panel). Mean difference is weight change (end point minus baseline) in the LES condition minus weight change in the sugar condition over the intervention period (a negative score favours LES). Squares represent mean difference in BW for the individual comparisons; square size is proportional to the weight of each comparison; horizontal lines represent 95% CIs; diamonds represent the summary estimates and 95% CIs from random effects models for comparisons in adults for LES versus sugar, adults and children for LES versus sugar, and adults for LES versus water. BW, body weight; LES, low-energy sweetener.CC BY · PubMed Central

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Research works printed but not linked: 3

  1. Reis TA, Goulart P, de Oliveira RME, Oliveira Ld, de Abreu PS, Azevedo Ad . Metabolic parameters of wistar rats subjected to diet supplemented with stevia and sugar. Semina: Ciéncias Agrarias (Londrina) 2011; 32: 1477–1488.
  2. EFSA. EFSA Panel on Food Additives and Nutrient Sources added to food. Scientific opinion on the safety of steviol glycosides for the proposed uses as a food additive. EFSA J 2010; 8: 1–84.
  3. Carvalho P, Sousa M, Barros R, Padrao P, Moreira P, Teixeira V . Impact of morning ingestion of sugary and sweetened beverages on energy and fluid intake throughout day. Ann Nutr Metab 2013; 63: 1448–1449.

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Metadata

Authors
Rogers, P. J., Hogenkamp, P. S., de Graaf, C., Higgs, S., Lluch, A., Ness, A. R., Penfold, C., Perry, R., Putz, P., Yeomans, M. R., & Mela, D. J.
Affiliations
  • University of Bristol (GB)
  • Uppsala University (SE)
  • University of Birmingham (GB)
  • Danone (France) (FR)
  • University Hospitals Bristol NHS Foundation Trust (GB)
  • University of Sussex (GB)
  • Unilever Research and Development Vlaardingen (NL)
ORCID
Venue
International Journal of Obesity
Publisher
Springer Science and Business Media LLC
Published
2015-09-14
Volume
40
Issue
3
Pages
381-394
ISSN
  • 0307-0565 (ISSN-L)
  • 1476-5497
DOI
10.1038/ijo.2015.177
PMC
PMC4786736
OpenAlex
W2171131656
Cited by
358
References
210
Citations by year
2026: 16 · 2025: 19 · 2024: 24 · 2023: 29 · 2022: 33 · 2021: 26 · 2020: 53 · 2019: 34 · 2018: 46 · 2017: 44 · 2016: 31 · 2015: 2
FWCI
5.26
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Obesity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion, cc-by)
  • Socio-Environmental Systems Modeling (acceptedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
Funders
  • University Hospitals Bristol NHS Foundation Trust
  • National Institute for Health and Care Research (NF-SI-0513-10083)
  • European Commission (607310)
  • University of Bristol
  • Wageningen University and Research
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
energy intake, body weight, body mass index, sugar-sweetened beverages, ad libitum feeding, energy density, weight gain, reverse causality, animal studies, prospective cohort, randomized controlled trials
MeSH terms
Animals, Body Weight, Energy Intake, Humans, Obesity, Sweetening Agents, Reproducibility of Results, Weight Gain, Body Mass Index, Randomized Controlled Trials as Topic, Evidence-Based Medicine, Models, Animal, Non-Nutritive Sweeteners, Observational Studies as Topic

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