EAL

NNNS: Appetite (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Tested the hypothesis that sweet taste per se would elicit cephalic phase insulin release (CPIR) in normal-weight men.

Inclusion Criteria:

Non-smokers
Normotensive
Free of metabolic disease
Stable body weight
Were non-restrained eaters
Had never followed an energy-restricted diet
Did not habitually use intense sweeteners.

Exclusion Criteria:

Description of Study Protocol:

Recruitment

Approved by the institutional review board of the University of Paris-Nord. Subjects gave written consent before the experiment and were compensated for completing the study protocols.

Design

Subjects arrived at the laboratory on the evening before the test day. They consumed a standard dinner between 8:00 p.m. and 8:30 p.m. Dinner consisted of ham, green beans, hard cheese, stewed apples and bread. Water was provided ad libitum.
Test day

8:00 a.m.: Subjects consumed a standard carbohydrate-free breakfast composed of ham, eggs and coffee. Breakfast composition was intended to stabilize basal concentrations of hormones and metabolites throughout the experimental period. The amount of food provided for dinner and breakfast during the three sessions was determined by the amount consumed on the first occasion.
10:30 a.m.: Catheter was inserted into antecubital vein of each subject. Continuous blood drawing began 50 min before the oral presentation of the stimulus.
12:00 p.m.: Tablets were administered.

Tablets were neither seen nor touched and were placed in their mouths by the investigator. Subjects were instructed to suck on the tablets for five minutes. Compliance was verified by the investigator. The order of presentation of the three tablets was counterbalanced across subjects. All subjects participated in three tasting sessions, scheduled exactly one week apart.
Within-subject double-blind placebo controlled study.

Stimuli consisted of three carbohydrate-based tablets with no added flavor
Sucrose tablet contained three grams pure sucrose
Aspartame tablet: Three grams polydextrose and 18mg aspartame, matched for sweetness with the sucrose tablet in the pilot study
Placebo tablet: Three grams polydextrose (a bland-tasting carbohydrate not absorbed in the small intestine)

Blinding Used

Within subject double-blind placebo controlled study.

Statistical Analysis

The procedure used to separate cephalic-phase secretions from basal fluctuations in plasma glucose, insulin and glucagons concentrations was based on adjusted plots of sinusoid function (EASYPLOT; Spiral Software, Brookline, MA).
Analyses of plasma glucose, insulin and glucagons concentrations were based on residual values. Repeated-measures analysis of variance (ANOVA) was used with stimulus type and time as within-subject factors. Plasma concentrations of fatty acids were calculated and then compared by using repeated measures of ANOVA with stimulus type and period as within-subject factors.

Data Collection Summary:

Timing of Measurements

VAS (Visual analog scales): After sucking on the tablet, subjects were asked to rate the perceived intensity along a 100mm horizontal line, anchored with the French translation of "not sweet" at the left end and "very sweet" at the right end.
Blood collection: A specially designed double-lumen catheter was used to withdraw blood continuously at a constant flow of two milliliters per minute and without an anti-coagulant. Blood was drawn from 45 minutes before to 25 minutes after the oral presentation of the stimuli. 70 blood samples collected at one-minute intervals were obtained with a fraction collector.
Plasma measurements: Plasma assays for glucose, insulin, glucagons and fatty acids followed standard procedures. Glucose concentrations were measured by an enzymatic assay with glucose-oxidase technique; insulin and glucagons concentrations by a radioimmunologic method; fatty acids by colorimetric enzymatic method.

Description of Actual Data Sample:

Initial N: 12 normal healthy men
Age: 18 to 27 years
Anthropometrics: BMI 20-24kg/m².

Summary of Results:

Sweetness Rating

Sweetness ratings were 74.0±6.2mm for sucrose, 57.0±4.5mm for aspartame and 13.0±3.4mm for polydextrose placebo tablet.
Sucrose and aspartame tablets were rated as sweeter than placebo tablet (P<0.001).
The sucrose tablet was rated as sweeter than the aspartame tablet (P<0.05).

Plasma insulin

The ANOVA of residual values over the entire 70-minute period showed no effect of stimulus type, but a significant main effect of time (P<0.01) and a stimulus by type by interaction (P<0.01).
Analysis of the post-exposure period showed an effect of time (P<0.01) and a stimulus type by time interaction (P<0.01).

Comparisons of Single Residual Post-Exposure Time Points With the Baseline Mean

Sucrose condition: The residual insulin concentration decreased significantly eight to 10 minutes post-exposure (P<0.01). Residual insulin increased after 19 minutes post-exposure, though only the value at 22 minutes was significantly different from baseline (P<0.05). A decrease in pasma insulin was observed after the exposure to the aspartame tablet. This was significant 11 minutes to 13 minutes post-exposure (P<0.01). In the placebo, a significant decrease in insulin concentration was observed nine minutes and 12 minutes post-exposure (P<0.05) and 23 minutes to 45 minutes post-exposure (P<0.05).

ANOVA of insulin AUCs showed a main effect of phase (P<0.01) and a stimulus type-by-phase interaction (P<0.05).

Calculated Areas Under the Curve for Plasma Glucose, Insulin and Glucagon Concentrations During Pre- and Post-Absorptive Periods¹

Sucrose Pre-Absorptive
Sucrose Post-Absorptive Aspartame Pre-Absorptive Aspartame Post-Absorptive Placebo Pre-Absorptive Placebo Post-Absorptive

Glucose AUC (N=8) (mmol min/L) -1.34±0.55 0.27±0.29^a -1.06±0.45 -0.73±0.38^b -1.37±0.55 -0.67±0.48^b

Insulin AUC (N=12) (pmol min/L) -46.8±16.6 48.4±22.4^a -38.8±23.0 -0.5±10.4^a,b -28.9±32.3 -30.6±12.8^b

Glucagon AUC (N=12) (ng min/L) -95±283 -38±93 105±90 95±90 -94±157 -74±52

1: Means ±SEM with different superscript letters are significantly different P<0.05

Plasma glucagons: Over the entire 70 minutes, there were no significant effects of stimulus, type, time or stimulus type by time interaction.

Plasma glucose: There was no cyclical pattern in basal plasma glucose. The ANOVA of residual values over the entire 70 minutes showed that only time had a significant effect (P<0.05).

Comparisions within each condition showed significant differences of some residual post-exposure values and baseline.

Sucrose condition: Plasma glucose values decreased relative to baseline at seven, 13 and 17 minutes post-exposure (P<0.05). The glucose concentration then rose, reaching a peak at 25 minutes post-exposure, but only the value at 23 minutes was significantly different from baseline (P<0.05). A fall in plasma glucose was observed in the aspartame condition. But only values at 13 and 24 minutes post-exposure were significantly different from baseline (P<0.05). No rise in plasma glucose seen in this condition.

Placebo condition: Drop in plasma glucose was significant at one minute (P<0.01) and two, eight, 20 and 21 minutes post-exposure (P<0.05). No rise in plasma glucose was observed.

ANOVA of glucose AUCs showed, during the post-exposure phase, a main effect of phase (P<0.01) and a stimulus type-by-time interaction (P<0.05).

Fatty acids: No effect of stimulus type nor of period and no stimulus type-by-period interaction.

Author Conclusion:

Limitations

The way in which the non-flavored tablets was provided without being seen or touched induced stress and led to the inhibition of insulin pulsatility as well as CPIR.

No CPIR and no significant effect on plasma glucagons or fatty acid concentrations were observed after the three stimuli. There was a significant decrease in plasma glucose and insulin after all three stimuli. Only the consumption of the sucrose tablet was followed by a post-absorptive increase in plasma glucose and insulin after all three stimuli. Only the consumption of the sucrose tablet was followed by a post-absorptive increase in plasma glucose and insulin concentrations starting 17 and 19 minutes, respectively, after the beginning of sucking.

The results of the experiment showed that sweet taste provided in the form of sweet tablets did not elicit CPIR. Plasma glucose, insulin, glucagons and fatty acids were not modified after aspartame or sucrose tablets, compared with the non-sweet polydextrose tablet. The study suggests that sweet taste, per se, is not a sufficient stimulus for eliciting CPIR.

Funding Source:

Industry:

Searle France

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

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? N/A

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%.) N/A

4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A

4.4. Were reasons for withdrawals similar across groups? N/A

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? N/A

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? N/A

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? N/A

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? Yes

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? No

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? No

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

	Sucrose Pre-Absorptive	Sucrose Post-Absorptive	Aspartame Pre-Absorptive	Aspartame Post-Absorptive	Placebo Pre-Absorptive	Placebo Post-Absorptive
Glucose AUC (N=8) (mmol min/L)	-1.34±0.55	0.27±0.29^a	-1.06±0.45	-0.73±0.38^b	-1.37±0.55	-0.67±0.48^b
Insulin AUC (N=12) (pmol min/L)	-46.8±16.6	48.4±22.4^a	-38.8±23.0	-0.5±10.4^a,b	-28.9±32.3	-30.6±12.8^b
Glucagon AUC (N=12) (ng min/L)	-95±283	-38±93	105±90	95±90	-94±157	-74±52

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?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?	N/A
	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?	N/A
	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?	N/A
	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?	Yes
	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?	No
	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?	No
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