HTN: Caffeine (2007)

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

To investigate the tolerance phenomenon in both central (cerebral blood flow, mood, cognitive funtion) and peripheral (blood pressure, heart rate) effects of seven days of caffeine consumption (200mg twice per day), compared to seven days of placebo.

Inclusion Criteria:
Not clearly specified. Participants described as healthy, left-hemisphere dominant, daily caffeine consumers (180mg to 500mg per day), aged 23-38 years, with no relevant medical history, not taking any regular medication and non-smoking.
Exclusion Criteria:
Not mentioned.
Description of Study Protocol:
  • Recruitment: Not described
  • Design: Randomized, double-blind, crossover trial
  • Blinding used: Double-blind
  • Intervention: Seven days of caffeine-free diet (participants were free-living), supplemented with either 200mg caffeine or placebo twice per day. Final capsule taken on the morning of the study day, one hour before attending the research unit. 

Statistical Analysis

  • Differences between serial measurements were analyzed by summary measures
  • Area under the curve (AUC) by the trapezoidal method and maximum response after the caffeine challenge were calculated for the responses of each individual
  • Group means were compared by paired Student's T-tests.
Data Collection Summary:

Timing of Measurements

  • At the end of each seven-day period and after an overnight fast, participants arrived at the research unit at 9:00 a.m., one hour after taking the last caffeine capsule
  • Subjects completed a questionnaire scoring the the strength of 32 symptoms relating to caffeine-withdrawal and a retrograde cannula was inserted into the dorsum of the non-dominant hand
  • Baseline measurements were then taken of: Heart rate and blood pressure, brain blood flow, mood, four-choice reaction time and visual information processing tests. A blood sample was taken for subsequent caffeine measurement.
  • Subjects then consumed a cup of decaffeinated coffee containing 200mg caffeine, all measurements were then repeated at 30-minute intervals for the next two hours with blood glucose concentrations measured every 15 minutes
  • Blood sugar was maintained above 4.0mmol per L by ingestion of three to six grams of glucose when blood glucose fell below 3.9mmol per L.

Dependent Variables

  • Blood caffeine concentration (enzyme immunoassay technique)
  • Caffeine withdrawal symptoms (caffeine withdrawal questionnaire scores)
  • Brain blood flow or middle cerebral artery blood velocity (transcranial Doppler technique)
  • Heart rate (automated device)
  • Blood pressure (automated device)
  • Mood (UWIST mood score)
  • Four-choice reaction time
  • Visual change detection (visual information processing tests)
  • Visual movement detection (visual information processing tests).

Independent Variables

Daily caffeine intake of 200mg twice per day or placebo.

Description of Actual Data Sample:
  • Initial N: 14 subjects; seven males, seven females
  • Attrition (final N): 14; no mention of attrition
  • Age: 23 to 38 years
  • Ethnicity: Not specifically mentioned
  • Other relevant demographics: Not mentioned
  • Location: The University of Edinburgh, Scotland.
Summary of Results:
  • After the caffeine challenge, middle cerebral artery blood velocity decreased significantly in both conditions
  • Area under the curve for change in systolic blood pressure against time was significantly greater after caffeine challenge in those who had received placebo for seven days, compared to those who had received seven days of caffeine doses
  • Mood was most affected by caffeine status prior to the caffeine challenge.

Variable Result of Caffeine Challenge After 7 Days of Placebo Result of Caffeine Challenge After 7 Days of 200mg Caffeine Twice per Day P-Value for Difference from Placebo
Initial mean (95% confidence interval) change in systolic blood pressure in mmHg +8.7 (2.1, 13.4) +4.5 (0.8, 8.3) 0.13
Initial mean (95% confidence interval) change in diastolic blood pressure in mmHg +5.5 (3.2, 8.6) +1.1 (-0.8, 3.0) <0.005
Mean (95% confidence interval) change in cerebral artery blood velocity in cm/sec -8.0 (-10.0, -6.1) -4.9 (-6.8, -2.9) <0.02
Mean (95% confidence interval) change in Mood

Tense: -1.1 (-2.6, -.034)
Energetic: Not provided
Hedonic: Not provided

Tense: -4.7 (-7.5, -1.9)
Energetic: Not provided
Hedonic: Not provided

Tense: <0.02
Energetic: 0.24
Hedonic: 0.51

Mean (± standard error) reaction time improvement in s 0.02±0.01 0.02±0.01 Not provided

Visual change detection

No improvement No improvement N/A
Visual movement detection No improvement No improvement N/A
Mean (± standard error) plasma caffeine in mg/L 4.08±1.18 5.41±1.45 <0.02
Area under the curve for change in systolic blood pressure (Graphically depicted) (Graphically depicted) <0.04
Area under the curve for change in systolic blood pressure (Graphically depicted) (Graphically depicted)

0.055

Other Findings

Heart rate was unaffected by prevailing caffeine status.

Author Conclusion:
  • While history of exposure to caffeine will influence the effect of a dose, tolerance to this drug's vascular effects is incomplete both centrally and peripherally
  • In contrast, tolerance was not demonstrated in performance nor improvements in positive aspects of mood
  • Identifying these effects on a larger populations' health requires careful further investigation.
Funding Source:
University/Hospital: Bournemouth Hospital, University of Edinburgh
Reviewer Comments:
  • The abstract states that 12 volunteers were randomized, but the text states there were 14 with no mention of drop-outs
  • No description is given on how they confirmed compliance with the seven-day caffeine or placebo protocol, nor did they address how they knew participants truly consumed a caffeine-free diet.
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? No
  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? No
  1.3. Were the target population and setting specified? No
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? No
  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? 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) 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? 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? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  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? No
  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? 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? 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? N/A
  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? No
  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)? N/A
  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? 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