Mattes RD and Popkin BM. Nonnutritive sweetener consumption in humans: Effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr. 2009; 89: 1-14.

PubMed ID: 2643923
Study Design:
Narrative Review
R - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To examine the effects of non-nutritive sweetener consumption on appetite and food intake in humans and animal models and the potential mechanisms responsible.

Inclusion Criteria:

None identified.

Exclusion Criteria:

None identified.

Description of Study Protocol:

Statistical Analysis

None used.


Data Collection Summary:

Timing of Measurements

None identified.

Dependent Variables

  • BMI
  • Appetite
  • Food intake.

Independent Variables

  • Non-nutritive sweetener (NNS) ingestion
  • Nutritive (NS) ingestion.


Description of Actual Data Sample:

Initial N

Several dozen studies were referenced in this narrative review but no exact number was given, nor were there any tables displaying a summary of data or findings.

Summary of Results:

Consumption Levels of NNS and Association between Consumption of NNS and Appetite, Energy Intake and BMI


Primary Findings

Consumption levels of NNS

  • Since manufacturers are not required to provide content information, there is no direct measurement of use
  • From 2003 to 2004, 15.1% of the American population reported that they consumed foods or beverages containing NNS
  • Consumption of NNS is increasing. In the American population, from 1998 to 2004, there was a 6.9% increase in NNS beverage consumption and an 81.2% increase in consumption of foods with NNS. Amount of NNS consumption has increased 37.7% and 14.2%, respectively.

NNS and appetite

  • Earlier reviews report that acute exposure to NNS via non-energy-yielding vehicles augments hunger and that the sweetness of NNS enhances post-ingestive hunger. This has been found to be true of sodium chloride as well and now it is believed that, in general, oral exposure to a palatable stimulus in the absence of energy increases hunger.
  • NNS have no effect on hunger when administered via nasogastric tube or capsules, indicating that changes in hunger may be due to orosensory stimulation. It is unclear if this translates to increased energy intake.
  • When NNS are incorporated into energy-yielding foods or are part of a meal, no increase in hunger is evident.

NNS and energy intake

  • It has been hypothesized that carbohydrate replacement (not addition) with NNS results in a relative increase in fat and protein consumption. However, in free-living individuals NNS are used as additions to the diet and not substitutions as evidenced by overall increased contribution of carbohydrate in the diet (as a percent of energy intake).
  • The majority of evidence indicates that NNS have no short-term effects on energy intake
  • Longer-term feeding trials generally indicate that the use of NNS result in no change or a reduction in energy intake (incomplete compensation).


  • Intervention trials fail to document that NNS promote weight gain
  • Observational studies are equivocal. Some studies show increased risk of weight gain associated with increased consumption of NNS, while others show that consumption of NNS facilitates weight management in individuals who have previously lost weight.
  • There are many methodological differences amongst various studies, thereby confounding results and making comparisons among studies difficult.

Mechanisms of NNS and weight management

  • NNS serve to maintain palatability of foods that are low in energy
  • No data indicate that NNS modify energy balance independently of their influence on energy intake
  • NNS, when substituted for NS, results in decreased carbohydrate intake; however most NNS are additions to the diet and not substitutions.

Mechanisms of NNS and appetite stimulation

  • Cephalic phase stimulation: Neurally mediated physiological responses to prime the body to optimize digestion. Researchers disagree as to how cephalic stimulation affects hunger. The role of NNS is unclear and supportive evidence that NNS increase hunger via this mechanism is unsubstantiated.
  • Nutritive and osmotic effects: Changes in the osmotic and nutrient properties of foods and beverages through substitution of NNS for NS has not been shown to affect satiety
  • Gut peptide response: Failure of NNS to release peptides that augment satiety may result in increased energy intake; however, some NNS elicit the release of satiety peptides (sucralose) while others (aspartame) do not
  • Palatability: NNS increase palatability which may result in over-consumption. Additionally these foods may be viewed as “healthy” and over-consumption may occur; however, there is inconclusive evidence that palatability influences absolute energy intake.

Theoretical mechanisms by which NNS may enhance energy intake or balance

  • Loss of signal fidelity
  • Activation of reward systems
  • Training the palate to like sweetness
  • None of these theories have been satisfactorily evaluated and no substantial evidence exists to support that NNS increases energy intake in free-living individuals.



Author Conclusion:
  • The safety of NNS has been established but their influence on appetite, energy intake and body weight has not been fully characterized
  • Recent studies show that when incorporated into energy-containing foods NNS do not cause an increase in hunger
  • Longer-term feeding studies show an incomplete compensation of energy of 5% to 15% when replacing NS with NNS; however, clear evidence of improved weight maintenance in free living individuals is still lacking
  • NNS have been thought to exacerbate the problem of positive energy balance; however, none of the mechanisms by which NNS may do so have been adequately substantiated by available evidence
  • There is no clear evidence that NNS augments appetite via stimulation of cephalic phase responses, altering osmotic balance or enhancing food palatability
  • There is emerging evidence that selected NNS may stimulate the release of satiety hormones
  • Use of NNS likely promotes a preference for higher sweetener levels of foods and beverages, but it is unclear if this leads to increased energy intake
  • When used as substitutes for NS, not additions to the diet, NNS have the potential to aid in weight management, but it is unclear if they are used in this way
  • More studies in free-living populations are warranted to clarify NNS patterns of use.
Funding Source:
Other: None (review)
Reviewer Comments:

This review is comprehensive and interesting to read; however, it is highly ambiguous and makes no conclusive statements regarding the topic. There is no table to summarize reviewed research results.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes