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

P J Rogers, P S Hogenkamp, C de Graaf, S Higgs, A Lluch, A R Ness, C Penfold, R Perry, P Putz, M R Yeomans, D J Mela, P J Rogers, P S Hogenkamp, C de Graaf, S Higgs, A Lluch, A R Ness, C Penfold, R Perry, P Putz, M R Yeomans, D J Mela

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.

Figures

Figure 1
Figure 1
Flow of information through the different phases of the systematic review.
Figure 2
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 3
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 4
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.

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