EAL

EE: Ephedra (2005)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the extent to which daily administration of capsules containing a green tea extract would stimulate thermogenesis and increase daily EE
To determine whether the effects of the green tea extract on the metabolic rate and substrate oxidation in humans would be greater than that explained by its caffeine content.

Inclusion Criteria:

Understand and give written consent
Healthy, young men (volunteers) (determined by medical and nutritional histories)
Body fat ranging from lean to mildly obese (8-30% body fat).
Consume a typical Western diet, with fat contributing 35-40% of dietary energy intake
Estimated intake of methylxanthines (mostly as caffeine-containing beverages) ranging from 100 to 200 mg/d.

Exclusion Criteria:

Refusal to consent
Smokers
Competitive athletes and persons who engaged in intense physical activities
History of weight loss
Not healthy per medical history.

Description of Study Protocol:

Spent 24 h in respiratory chamber on 3 separate occasions; administered in a double-blind design; with 5-10 d interval between successive 24-h trials for each subject; Energy intake, nutrient content of the diet, sedentary lifestyle (reading, listening to radio, watching TV, etc), pattern of physical activity, meal pattern, and time period for sleeping remained the same
Randomly assigned to receive 1 of the following 3 treatments orally (in capsule form) 3 times/d (i.e., 2 capsules with breakfast, lunch, and dinner:
1. A green tea extract containing 50 mg caffeine and 90 mg epigallocatechin gallate (provided daily a total of 150 mg caffeine and 375 mg catechins; 270 mg was epigallocatechin gallate)
2. 50 mg caffeine, or
3. A placebo that consisted of cellulose as inert filler.

ANTHROPOMETRIC

Ht measured? Yes
Wt measured? Yes
Body fat determined: By the method of Durnin and Womersley (1974) from measurements of skinfold thicknesses taken at 4 sites
Fat free mass (FFM)? Calculated as the difference between body weight and body fat.

CLINICAL

Monitored heart rate? Yes, during the first 8 h of each trial with a portable frequency monitor
Body temperature? Not mentioned.

Resting energy expenditure

IC type: Stated that details described previously (1996)
Equipment of Calibration: Cited previous description
Coefficient of variation using std gases: Not described
Rest before measure (state length of time rested if available): Not applicable due to 24 h measure
Measurement length: Continuously monitored during stay in respiratory chamber (24 hr x 3)
Steady state: Not applicable; measured heart rate
Fasting length: No methylxanthine-containing foods or beverages were consumed 24 h before or during the stay in the respiratory chamber.
Exercise restrictions: During each of the subject’s 3 respiratory chamber trials, remained the same
Room temp: Constant and comfortable temperature
No. of measures within the measurement period: States “continuous during stay in respiratory chamber”
Were some measures eliminated? Not mentioned
Were a set of measurements averaged? Yes, EE during diurnal, nocturnal and total 24-h period
Coefficient of variation in subjects measures? Measurements of EE and the respiratory quotient (RQ) were accurate within 1-2%
Training of measurer? Not mentioned
Subject training of measuring process? Not mentioned.

DIETARY

During the study period (5-6 wks), the subjects were prescribed a weight-maintenance diet consisting of ~13% of energy as protein, ~40% as fat, and ~47% carbohydrates. “Diet” was 1.4 times the estimated basal energy requirements of the subject, predicted from the regression equation of Cunningham.

Data Collection Summary:

Independent variables of weight, height, age, BMI,and fat-free mass, fat mass
24-h EE, RQ
Urinary nitrogen and catecholamines
Calculated CHO, Pro, Fat Oxidation rates

Blinding used: Yes.

Description of Actual Data Sample:

N=10 healthy men
Mean age, y: 25±1 (SEM).

Statistical tests

Repeated-measures ANOVA used to determine significance. When statistically significant differences were detected, a post hoc pairwise comparison across treatments was performed by using Tukey’s test. Significance est. as P<0.05.

Summary of Results:

ANTHROPOMETRIC

Men	Mean±SEM
Wt, kg	78.7±4.3
Ht, cm	177±3
BMI	25.1±1.2
% Body fat	18.2±1.8
Fat-freebody mass, kg	63.8±2.5

TREATMENT RESULTS

Significant differences across treatments were found during the diurnal, nocturnal, and total 24-h periods (from 0.88 to 0.85; P<0.001). Treatment with the green tea extract yielded significantly (P<0.05) lower values than did the other 2 treatments (placebo and caffeine) during all 3 periods.

RQ RESULTS

Individual changes indicated that the RQ in most of the subjects (8 of 10) was substantially lower (differences >0.01) after the green tea extract than after the placebo; in 4 subjects the difference was =0.04. However, no correlation was observed between the magnitude of reduction of RQ and the degree of fatness (BMI or %body fat).

Energy expenditure during diurnal, nocturnal, and total 24-h (presented as Means ±SEM)

	*Diurnal EE, kJ (kcals)*	*Nocturnal EE, kJ (kcals)*	*Total 24-h periods, kJ (kcals)*
Placebo	6463±386 (1545±92)	3075±149 (735±36)	9538±521 (2279±125)
Caffeine	6547±383 (1565±92)	3053±148 (730±36)	9599±518 (2294±124)
Green tea	6754±352(1614±84)*	3112±140 (744±34)	9867±488 (2358±117)**

*, ** Significant differences across treatments

Diurnal EE was higher during treatment with the green tea extract than during treatment with placebo or caffeine, by 4.5% and 3.2%, respectively, but significantly (P<0.05) for the green tea extract only (*).
Total 24-h EE with the green tea extract was significantly (P<0.05) higher than that with both the placebo and caffeine (**), by 3.5% and 2.8%, respectively.
There were no significant differences in diurnal, nocturnal, or total 24-h EE between the caffeine and placebo groups.
There was an increase in 6 of 10 subjects after treatment with the green tea extract, ranging from 266 to 836 kJ (63.5 to 200 kcal).
No correlation was observed between the magnitude of thermogenic response and the degree of fatness (BMI or %body fat) of the subjects.

Urinary excretion of catecholamines

Urinary epinephrine and dopamine (its precursor) were not significantly different across treatments in any of the 3 periods.
Differences across treatments were only significant for total 24-h norepinephrine.(F=3.96, P<0.05).

Author Conclusion:

As stated by the author in body of report:

“In our study, 24 h E, RQ, and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men."
“Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P<0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P<0.001) without any change in urinary nitrogen."
"Twenty-four h urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P<0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines.”
“Stimulation of thermogenesis and fat oxidation by the green tea extract was not accompanied by an increase in heart rate. In this respect, the green tea extract is distinct from sympathomimetic drugs, whose use as an anti-obesity thermogenic agents is limited by their adverse cardiovascular effects and, hence are particularly inappropriate for obese individuals with hypertension and other cardiovascular complications.”
“In conclusion, oral administration of the green tea extract stimulated thermogenesis and fat oxidation and thus has the potential to influence body weight and body composition via changes in both EE and substrate oxidation.”

Funding Source:

Government:

Swiss National Science Research Fund

Industry:

Arkopharma Laboratories

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

University of Geneva, Geneva University Hospital

Reviewer Comments:

[Use of room respirator with indirect calorimetry and provided TOTAL energy expenditure that is a different outcome than RMR; Not used in Conclusion Statement Grade].

Strengths

Random assignment with double blinding to treatments; decreases the effect of researcher bias
Measured height and weight with skinfold thicknesses taken at four sites for body fat
5-10 days between treatments (wash-out period) to minimize the effects of the previous treatment on the present treatment.

Limitations

Small sample size; no power calculation
Limited generalizability; sample consisted of 10 healthy non-obese young men May not be generalizable to women or individuals who engaged in intense physical activities or had a history of weight loss
Volunteers (self-selection bias?)
Lack of details of IC; accuracy (indicated discussed in previous published article).

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?	N/A
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	N/A
	1.3.	Were the target population and setting specified?	N/A
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?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	N/A
	2.4.	Were the subjects/patients a representative sample of the relevant population?	N/A
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?		No
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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?	N/A
	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.)	N/A
	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?	N/A
	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?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	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?	N/A
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	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?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	N/A
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	N/A
	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?	N/A
	8.2.	Were correct statistical tests used and assumptions of test not violated?	N/A
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	N/A
	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)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	N/A
	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?	N/A
	9.2.	Are biases and study limitations identified and discussed?	N/A
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.2.	Was the study free from apparent conflict of interest?	N/A