EE: Ephedra (2005)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The objective of this study was to

  1. Examine the effect of smoking and caffeine consumption separately and concurrently to determine if these agents together exert a more profound thermic effect than either alone.

Definitions

  • Steady state: After arrival and after rest for at least 30 min, for baseline REE, continuous REE was monitored until it plateaued; followed by 30 min measurement of REE (30 min resting baseline).
Inclusion Criteria:
  1. Understand and give written consent
  2. Smokers--smokers were cigarette smokers for at least one year, actively smoking at the time of the study with at least one pack-year history and also regular caffeinated coffee drinkers
  3. Male adult between ages 18 and 65 yrs of age; volunteers
  4. Nonsmoking control-lifetime nonsmokers and regular caffeinated coffee drinkers
  5. Volunteers
  6. Without known cardiopulmonary disease, diabetes or thyroid dysfunction (examined by physician)
  7. Not on medications that affect metabolic rate such as beta-blockers, decongestants, or sedatives.
Exclusion Criteria:
  1. Refusal to consent
  2. Not meeting inclusion criteria.
Description of Study Protocol:
  • Testing protocols were randomly administered to each subject.

Smokers

  1. Placebo tablet
  2. Caffeine 200 mg: A 200 mg caffeine tablet was ingested (instead of placebo).
  3. Placebo and 1R4F Cigarettes: Subject smoked an additional 1R4F cigarette at 60 and 90 min after the initial 2 cigarettes.
  4. Caffeine 200 mg and 1R4F Cigarettes: A 200 mg caffeine tablet was ingested; Cigarettes as #3 during metabolic testing period.

Control Group

  • The nonsmoking control group underwent testing protocols #1 and 2.

ANTHROPOMETRIC

  • Ht measured? Yes, method not described
  • Wt measured? Yes, method not described
  • Body fat? Body fat measurement via the multiple skin-fold technique.

CLINICAL

  • Monitored heart rate? Not mentioned
  • Body temperature? Not mentioned
  • Medications administered? Placebo (lactose) or caffeine (see protocols below).

Resting energy expenditure

  • IC type: Open metabolic cart with mask
  • Equipment of Calibration: Not mentioned
  • Coefficient of variation using std gases: Not mentioned
  • Rest before measure: At least 30 min. prior to initial measurement followed by 20 min rest and during 3 h testing periods, 10 min between REE measurements
  • Measurement length: 30 min baseline after steady state; After 20 min initial break, 3 hr measurement period. (see protocols)
  • Steady state: After arrival and after rest for at least 30 min, for baseline REE, continuous REE was monitored until it plateaued
  • Fasting length: Fasted prior 12 hr.
  • Exercise restrictions: No vigorous exercise 12 hr prior to testing
  • Room temp: Comfortable to subject
  • No. of measures within the measurement period: Reported as one minute averages; monitored continuously; 30 min baseline followed by 5 20-min periods during measurement period alternating with 10 min periods of resting quietly (120 min total)
  • Were some measures eliminated? Not mentioned
  • Were a set of measurements averaged? Yes
  • Coefficient of variation in subjects measures? Not mentioned
  • Training of measurer? Not mentioned
  • Subject training of measuring process? Yes, prior to testing including wearing the metabolic mask for a brief period of time.

Intervening factors

  • Age, % body fat and thermic effect of caffeine per kg/body weight).
Data Collection Summary:

Outcome(s) and other measures

  1. Body fat %
  2. Measured REE [(VO2, l/min), VCO2 (l/min; ml/kg/min)], RQ.
  3. Age, body fatness, smoking history.

Blinding used: No.

Description of Actual Data Sample:
  • N=16 volunteer males
  • Smokers: N=10 males; age 39.9±1.9 y
  • Nonsmokers Control: N=6 males; age 33.5±2.1 y.

Statistical tests

(Group means±SE.) Repeated measures multivariate analysis of covariance (MANCOVA) with two within-factors: treatment (4 levels) and time (5 levels). Repeated measures MANCOVA with 2 treatment within-subject factor and a 5 level time within-subject factor for nonsmoking group. Post-hoc Bonferroni analysis ( 95% CI;alpha = 0.05). T-tests; Partial correlations; P<0.05

  • Power analysis: ~ 6,000 subjects would be needed to have an 80% chance of detecting a small difference.
Summary of Results:

ANTHROPOMETRIC

  • Two-tailed t-tests indicated the groups were similar except for pack-years of smoking.

Male Smokers (n=10) Mean±SD

Wt, kg

69.9±0.7

Ht, cm

172.1±7.0
% Body fat 18.6±2.1

Pack years

20.4±3.5
Caffeine consumption, mg/d 371.4±77.5

REE, kJ/min (kcal/min)

5.1±0.03 (1.2±0.01)

Male Non-Smokers (n=6) Mean±SD

Wt, kg

71.7±1.3

Ht, cm

182.5±15.7

% Body fat

21.1±3.1

Pack years

0
Caffeine consumption, mg/d 150±56.5

REE, kJ/min (kcal/min)

4.8±0.08 (1.2±0.02)

INDIVIDUAL CHARACTERISTICS

REE & SMOKING

  • 30 mins after smoking 2 1R4F cigarettes, REE increased 3.9%; then, declined to 2% at 60 min.
  • A third cigarette was smoked 60 min after the beginning of the treatment period, increasing REE by 2.4%. Smoking a fourth cigarette 90 min did not further increase REE, but prevented the REE from declining further.
  • On average, smoking four 0.8 nicotine cigarettes increased REE by 3.3% over the 3-h measurement period.
  • Increases in total energy expenditure or in energy expenditure at each measurement period was not significantly different from the resting baseline period.

CAFFEINE

  • Consuming 200 mg of caffeine produced a slightly higher acute increase in REE (4.3%) than smoking 2 cigarettes did. REE gradually increased (P<0.05) to a maximum 6.0% above baseline 2 hr after ingestion. Nonsmokers had significant (P<0.05) increases in REE compared to baseline at all measurement periods, and the overall increase was 6.7%.
  • Nonsmoking controls had a greater increase in REE than the smokers, but not statistically significant.

SMOKING AND CAFFEINE

  • Consuming 200 mg of caffeine and smoking 2 1R4F cigarettes initially (the first 30 min) increased REE more than either agent separately, and more than the separate effects combined.
  • An additive effect was noted, with the cumulative and individual measurements approximately equaling the sum of the thermic responses to the individual agents.
  • Combined mean increase in REE over the 3 h measurement period was 7.5% (P<0.05). The total increase in REE measured was significant at all but the last measurement period.
  • In the smokers, no significant correlation was found between percent body fat and the thermic response to caffeine. Controlling for the amount of caffeine consumed routinely produced a nonsignificant relationship between body fat and the thermic effect of caffeine.
  • When controlling both for the amount of caffeine routinely consumed and pack-years of smoking, a significant relationship between body fatness and the thermic response 30 min following caffeine consumption was detected (R=0.65, P=0.02).
Author Conclusion:

“Consumption of 200 mg of caffeine in the fasted condition increased REE of the smokers by 4.8% over 3 hr. Smoking four 0.8 mg cigarettes and ingesting 200 mg caffeine significantly increased REE by 7.5% over the 3 hr measurement period.”

“Caffeine increased REE in the non-smoking controls 6.7%; nonsignificantly different from results obtained on smokers. Fasted and non-smoking (baseline) REE was similar in smokers and non-smoking control subjects.”

“We observed a slightly smaller increase in REE following consumption of caffeine in the smoking group compared to the nonsmoking group. The nonsmoking group chronically consumed less caffeine than did the smokers, and may have been relatively caffeine-naïve compared to the smokers... and… cigarette smoking enhances the elimination of many drugs, particularly theophylline (similar to caffeine)."

"Cigarette smokers may have exhibited a blunted response because of their higher routine caffeine consumption. Partial correlation analysis revealed a positive correlation when controlling for both factors suggests such an interaction exists, blunting the thermogenic response from caffeine in chronic smokers.”

“Combining cigarette smoking and caffeine consumption accelerates the clearance of caffeine... effects of smoking are entirely acute, rather than chronic in origin.”

“REE range was -0.7% to +9.2%; mean of 3.3% over a 3 h measurement period.”

“Effects of smoking and the effects of caffeine on REE are additive [and] there was a supra-additive response following the first cigarettes of the day."

"Failure to observe the energy expenditure over a longer period of time would have resulted in a misleadingly high thermic response to caffeine consumed with cigarette smoking. The 7.5% cumulative increase in energy expenditure over 3 hr more realistically reflects the metabolic consequences of concomitant nicotine and caffeine ingestion. This effect would be lost with smoking cessation.”

“Overall, the relatively small increase in REE caused by the combined influences of caffeine and nicotine suggests that it probably does not contribute greatly to the rapid and often dramatic weight gain which follows smoking cessation."
Funding Source:
University/Hospital: University of Louisville
Reviewer Comments:

Strengths

  • Random administration of treatments and good description of treatment protocols.

Weaknesses

  • Small sample groups; power calculation indicated a sample size of app. 6,000 subjects would be needed to detect differences in resting baseline measurements
  • Generalizability: Sample restricted to relatively healthy males-smokers and nonsmokers; volunteers (self-selection bias); no females
  • Height and weight determination: Self-report or measured
  • Lack of description of IC calibration (accuracy)
  • Caffeine ingestion not restricted; large difference between smokers and non-smokers.
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? 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? 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? Yes
  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? No
  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? No
  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? No
  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