EE: Caffeine and Other Stimulants (2014)


Belza A, Toubro S, Astrup A. The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake. Eur J Clin Nutr. 2009; 63(1): 57-64.

PubMed ID: 17882140
Study Design:
Randomized Crossover Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate three different food ingredients [tyrosine, green tea extract (GTE) and caffeine] on:

  • Resting metabolic rate and hemodynamics
  • Ad libitum energy intake (EI) and appetite.
Inclusion Criteria:
  • Weight-stable ±3kg in the last three months
  • Non-smoking, non-athletic
  • Had no use of dietary supplements or frequent use of medication
  • Coffee intake that was low to moderate
  • Provided written informed consent.
Exclusion Criteria:
  • Rare use of hot spices
  • Avoided extreme intake of caffeine containing beverages such as coffee, tea, chocolate milk and some soft drinks.
Description of Study Protocol:


Healthy and normal-weight men (BMI 22.4±1.8kg/m2) were invited to participate in the study.


Randomized double-blind placebo controlled crossover trial.

Blinding Used

Double blind.


Treatments were separated by at least three days and were administered as either:
  • 500mg green tea extract (GTE)
  • 400mg tyrosine
  • 50mg caffeine
  • Placebo.

Statistical Analysis

  • All descriptive data are given in mean and standard deviation (SD)
  • All results are given in mean and standard error
  • The level of significance was set at P<0.05
  • Analyzes were performed using SAS 8.2
  • All data were analyzed with intent-to-treat analysis and the last observation was carried forward
  • Prior to statistical analysis all data were tested for normality by Shapiro-Wilk W-test and variance homogeneity and data transformed if necessary
  • Differences between supplements were tested by analysis of mixed linear models procedure as repeated measurement adjusted for baseline level, and with or without adjusting for other confounders.
    Post-hoc comparisons were made with Tukey-Kramer adjustment of significance levels for the pair-wise comparison using unpaired T-test when the analysis indicated significant treatment effects.
  • Differences between baseline levels were tested by analysis of mixed linear models procedure
  • Four-hour baseline subtracted values of RMR, RQ and VAS scores were also calculated as an area under the curve and difference between treatments tested by mixed linear models procedure.


Data Collection Summary:

Timing of Measurements

Measurements made before and after treatments, which were separated by at least three days.

Dependent Variables

  • Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured by indirect calorimetry using a ventilated hood system (indirect calorimeter was not described). RMR was calculated using a formula assuming a fixed protein catabolism. The precision of the ventilated hood was validated by an alcohol burning test on a weekly basis coefficient of variance was 1.5.
    • The measurements were of 4.5 hours duration from 8:30 a.m. to 1:00 p.m. hours
    • Before each measurement, participants rested for at least 30 minutes
    • Between 8:30 a.m. and 9:00 a.m. hours, a 25-minute baseline measurement was completed
    • At around 9:00 a.m. hours, participants ingested one of the four treatment compounds with 175ml tap water and 25-minute measurements were repeated eight times during the next four hours
    • Participants were instructed to fast except for water from 10:00 p.m. on the evening before, and had refrained from other habitual medication, alcohol and energetic physical activity for 24 hours
    • To limit diurnal variation and inter- and intra-subjects variability, subjects were measured on an identical schedule and at the same time of day.
  • Acute thermogenic response was measured for four hours following ingestion
  • Appetite measured through visual analogue scales (VAS) used to monitor each subject's appetite sensations before and after intake of the test compound. Subjects completed VAS before intake of the compound and at 10:00 a.m., 11:00 a.m., noon and 1:00 p.m.
  • Height and body weight were measured to the nearest 0.05kg on a decimal scale and height to the nearest 0.5cm
  • Blood pressure and heart rate were assessed at 8:30 a.m., 9:30 a.m., 10:30 a.m., 11:30 a.m., 12:30 p.m. and 1:00 p.m.
  • Ad libitum energy intake: Subjects were provided with ad libitum brunch, four hours after intake of one of the treatment compounds. Subjects were instructed to eat at a constant pace and to stop eating when they felt satiated. Ad libitum EI was assessed from the amount of the meal consumed.

Independent Variables

  • Treatments were separated by at least three days and were administered as:
    • 500mg green tea extract (GTE)
    • 400mg tyrosine
    • 50mg caffeine
    • Placebo.
  • Placebo tablets contained microcrystalline cellulose and could not be distinguished from the bioactive treatment
  • The treatments were similarly encapsulated and differed only with regard to the content of the individual bioactive ingredient or placebo vehicle.
Description of Actual Data Sample:
  • Initial N: 12 men
  • Attrition (final N): 12 men
  • Age: Mean age 23.7±2.6 years
  • Ethnicity: Danish
  • Anthropometrics: Mean BMI (kg/m2) 22.4±1.8
  • Location: Denmark.


Summary of Results:

Key Findings

  • Caffeine induced a thermogenic response of 6% above baseline value (72±25kJ per four hours, mean ±SE) compared to placebo (P<0.0001)
  • The thermogenic responses to GTE and tyrosine were not significantly different from placebo
  • Tyrosine tended to increase four-hour respiratory quotient by 1% compared to placebo (0.01±0.005, P=0.05)
  • Ad libitum EI was not significantly different between treatments but was reduced by 8% (-403 ±335kJ) compared to placebo after intake of tyrosine, GTE and caffeine
  • No significant difference in hemodynamics was observed between treatments.
Author Conclusion:

Only caffeine in the given dose was thermogenic and without causing any hemodynamic or other side effects. Although the reductions in ad libitum EI were not significant, they support previous findings. The small sample size can have prevented the detection of any appetite suppressant properties of the treatments and further investigation is required.

Funding Source:
Other: Science, Toxicology & Technology, San Francisco, CA, USA
Reviewer Comments:
  • Small sample size
  • Indirect calorimeter were not described.
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? No
  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? No
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? 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? Yes
  6.6. Were extra or unplanned treatments described? Yes
  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? ???
  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? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? N/A
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? No
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