EE: Caffeine and Other Stimulants (2014)


Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: A placebo-controlled, double-blind eight-week intervention in obese subjects. Int J Obes (Lond). 2007; 31(1): 121-130.

PubMed ID: 16652130
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate the effects of acute and sub-chronic effect of a supplement containing tyrosine, capsaicin, catechins and caffeine or placebo on thermogenesis, body fat loss and fecal fat excretion.

Inclusion Criteria:
  • Provided written informed consent
  • Were weight stable within ±3kg two months before the study inclusion
  • Non-smoking
  • Non-athletic
  • No daily use of medication except for anti-conception and anti-hypertensive compounds
  • Followed a normal Danish diet with no use of hot spices or extreme intake of dairy products or coffee and tea.
Exclusion Criteria:
Not described.
Description of Study Protocol:


Subjects were recruited by advertisements in the newspaper.


Randomized two-arm, parallel, placebo controlled trial.

Blinding Used

Double blind.


  • Overweight or obese subjects underwent an initial four-week hypocaloric diet (3.4mJ per day)
  • Those who lost more than 4% of body weight were instructed to consume a hypocaloric diet (-1.3mJ per day) and were randomized to receive either placebo or bioactive supplement
  • The bioactive supplement contained:
    • 1,500mg green tea extract (376mg catechins)
    • 1,218mg L-tyrosine
    • 302mg caffeine (150mg from green tea and 152mg anhydrous caffeine)
    • 450mg cayenne (1.2mg capsaicin is equal to 240,000 scoville heat units)
    • 3,890mg calcium carbonate (2,000mg elementary calcium).

Statistical Analysis

  • All results are given in mean and standard deviation (SD)
  • The level of significance was set at less than 0.05
  • Analyses were performed with SAS vs. 8.2
  • All data were analyzed on an intent-to-treat analysis
  • Before the analyses, all data were tested for normality with Shapiro-Wilk W-test and variance homogeneity and data transformed if necessary
  • Differences between supplements were tested by analysis of variance with or without adjusting for various confounders
  • Post-hoc comparisons were made with Tukey Kramer adjustment of significance levels for the pairwise comparison
  • The relationship between changes in four-hour RMR (AUC) and anthropometric and hemodynamic measures during the intervention was tested in a Pearson correlation test
  • Relationship between four-hour RMR and change in FM during the weight maintenance phase was tested by linear regression.
Data Collection Summary:

Timing of Measurements

The thermogenic effect of the compound was tested before and after eight weeks.

Dependent Variables

  • Body weight, waist-hip circumference and blood pressure were assessed before and after the low calorie diet phase (week four), at four weeks into the weight maintenance phase (week eight) and at completion (week 12)
  • Body weight was measured to the nearest 0.05kg on a decimal scale, height to the nearest 0.5cm and waist-hip circumference to the nearest 0.5cm
  • Heart rate and blood pressure were measured using an automatically inflating cuff. The subjects were instructed to fast 10 hours before each assessment.
  • Body composition, fat-free mass (FFM) and fat mass were estimated by bioelectrical impedance analysis using an Animeter before and after the low calorie diet (LCD) phase at weeks zero and four and at completion of week 12. DEXA scans were performed as whole body scans in the slow mode (45 minutes).
  • All subjects collected 24-hour urine during each feces collection period. Three tablets were taken with a total of 240mg 4-aminobenzoic acid (PABA) were taken at meal times as a biomarker of complete urine samples. Urine calcium concentration was measured using atomic absorption on a Spectra AA-200. Urinary content of catecholamines was determined using a commercial radioimmunoassay kit from Germany.
  • All subjects underwent assessments of resting metabolic rate and respiratory quotient by indirect calorimetry using a ventilated hood system (not described). The measurements were five hours in duration, from 8:00 a.m. to 1:00 p.m., and were conducted at initiation and completion of the weight maintenance phase.
    • Before each five-hour measurement, participants rested in a supine position for 30 minutes
    • Between 8:00 a.m. and 9:00 a.m. hours two baseline measurements (2 x 25 minutes) were assessed
    • Participants then ingested one third of the daily dose of medication 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. hours on the evening before
    • Subjects refrained from other habitual medication, alcohol and energetic physical activity for 24 hours before the two measurements
    • To limit diurnal variation, all measurements made on an identical time schedule
  • Thermogenesis, body fat loss, and fecal fat excretion: Subjects collected all feces throughout three consecutive days in one week before each respiratory measurement. All feces were collected in pre-weighed containers.

Independent Variables

  • Overweight and obese subjects underwent an initial four-week hypocaloric diet (3.4mJ per day)
  • Those who lost more than 4% of body weight were instructed to consume a hypocaloric diet (-1.3mJ per day) and were randomized to receive either placebo or bioactive supplement.
Description of Actual Data Sample:
  • Initial N: Ninety three subjects were initially recruited
  • Attrition (final N): Final N was 80 total (23 placebo group, 57 bioactive compound group)
  • Age:
    • Mean age in the placebo group: 51±10.5 years
    • Mean age in the bioactive group: 46.2±10.9 years.
  • Ethnicity: Danish
  • Other relevant demographics:
    • Mean fat mass in placebo group: 29.7kg±7.3kg
    • Mean fat mass in the bioactive group: 28.7kg±7.2kg.
  • Anthropometrics:
    • Mean BMI in the placebo group: 29.2±2.4kg/m2
    • Mean BMI in the bioactive group 84.2±10.9kg/m2.
  • Location: Denmark.
Summary of Results:

Key Findings

  • Weight loss during the induction phase was 6.8kg±1.9kg
  • At the first exposure the thermogenic effect of the bioactive supplement exceeded that of the placebo by 87.3kJ per four hours (95% CI: 50.9, 123.7, P=0.005); after eight weeks, this effect was sustained (85.5kJ per four hours, 95% CI: 47.6,123.4, P=0.03)
  • Body fat mass decreased more in the supplement group by 0.9kg compared with placebo (P<0.05)
  • The bioactive supplement had no effect on fecal fat excretion, blood pressure or heart rate.



Author Conclusion:

The bioactive supplement increased four-hour thermogenesis by 90kJ more than placebo, and the effect was maintained after eight weeks and accompanied by a slight reduction in fat mass. These bioactive components may support weight maintenance after a hypocaloric diet.

Funding Source:
Metabolife Inc, San Diego, California
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
  • Groups were not similarly sized
  • Indirect calorimeter was not described, giving questionable validity.
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? ???
  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? ???
  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? 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? 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? ???
  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? 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)? Yes
  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