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Study Title and Description
The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate?
Key Questions Addressed
| 1 | For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on cardiovascular outcomes? |
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Primary Publication Information
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| Title | The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate? |
| Author | MA Addicott,LL Yang,AM Peiffer,LR Burnett,JH Burdette,MY Chen,S Hayasaka,RA Kraft,JA Maldjian,PJ Laurienti, |
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| Year | 2009 |
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Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Cardiovascular Design
| Question... Follow Up | Answer | Follow-up Answer | |
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| What outcome is being evaluated in this paper? | Cardiovascular |
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| What is the objective of the study (as reported by the authors)? | We investigated the effects of caffeine on cerebral blood flow (CBF) in increasing levels of chronic caffeine use. |
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| Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods) | Participants: Forty-five adult volunteers (25 women, aged 18-50 years) participated in this study between 2005 and 2007. Potential volunteers were recruited from the Winston-Salem, North Carolina area with flyers, newspaper advertisements, and by word of mouth. Respondents who met the following inclusion criteria were invited to participate: 1) no history of migraines, diabetes, stroke, hypertension, or any neurologic or vascular disease, 2) no current symptoms of depression or an anxiety disorder, 3) no previous brain surgery or serious CNS trauma, 4) no use of vasoactive medications, 5) no current abuse of alcohol or illicit drugs, 6) visual acuity able to be corrected to 20/40, and 7) no MR incompatible implanted devices. Participants' average daily caffeine intake was estimated from their responses to a 7-day caffeine consumption diary (7-day CCD) modified from the Caffeine Consumption Questionnaire (CCQ) (Landrum, 1992) and from data on the caffeine content of common beverages (Center for Science in the Public Interest web site, www.cspinet.org, accessed July 1997). Participants were then identified by their daily caffeine use as "low users" (n =18; < 200 mg/day), "moderate users" (n = 9; 200 - 600 mg/day), and "high users" (n = 18;>600 mg/day). Study design: Each participant underwent quantitative perfusion imaging on four separate occasions in a randomized, double-blind study design. Test sessions were at least one week apart to allow participants to resume normal caffeine use between scans. Two of these scans followed participants' normal caffeine use (native state) and two followed abstention from caffeine (abstained state). For the native state, participants were instructed to continue their normal daily caffeine usage until 15 minutes prior to their scheduled visit. For the abstained state, participants were instructed to avoid consuming any foods, beverages, or drugs that contain caffeine for 30 hours prior to their scheduled visit. This duration of abstinence was selected so that caffeine concentrations would most likely be below detection threshold (0.2 ug/ml) at the time of testing. Caffeine use or abstention from use during the 30 hours before a scan visit was verified with a 3-day CCD. In addition, a saliva sample was obtained upon arrival to the scan visit to verify compliance with study requirements. Following the first saliva sample, participants ingested a capsule containing placebo or caffeine (250 mg, anhydrous). A second saliva sample was obtained 1 hour after drug administration to measure the varied levels of caffeine in each participant. Respiration rate, end-tidal CO2 , oxygen saturation (Capnocheck® II, SIMS BCI Inc., Waukesha, WI), heart rate, and blood pressure (IVAC vital check model 4410, ALARIS medical systems, Dublin, OH) were also recorded when the saliva samples were collected. Immediately following collection of the second saliva sample, participants were placed in the MRI scanner. |
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| How many outcome-specific endpoints are evaluated? | 3 |
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| What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) | Cerebral blood flow |
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| List additional health endpoints (separately). 2 | Heart rate |
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| List additional health endpoints (separately).3 | Blood pressure |
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| List additional health endpoints (separately).4 |
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| List additional health endpoints (separately).5 |
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| List additional health endpoints (separately).6 |
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| Clinical, physiological, other | Physiological |
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| What is the study design? | Controlled Trial |
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| Randomized or Non-Randomized? | RCT |
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| What were the diagnostics or methods used to measure the outcome? | Objective |
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| Optional: Name of Method or short description | Respiration rate, end-tidal CO2 , oxygen saturation (Capnocheck® II, SIMS BCI Inc., Waukesha, WI), heart rate, and blood pressure (IVAC vital check model 4410, ALARIS medical systems, Dublin, OH) were also recorded when the saliva samples were collected. |
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| Caffeine (general) | Caffeine (general) |
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| Coffee, Chocolate, energy drink, gum, medicine/supplement, soda, tea, other? |
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| Measured or self reported? | Measured |
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| Children, adolescents, adults, or pregnant included? | Adults |
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| What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) | Subjects were eventually all exposed to either placebo or caffeine. |
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| What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods) | There were expected differences between groups in daily caffeine use (mg/day) (p < 0.001; Bonferroni t -tests: low < moderate < high, p < 0.001) and in body-weight adjusted caffeine use (mg/kg/day) (p < 0.001; t -tests: low < moderate, p <0.05; low & moderate < high, p < 0.001). Differences between groups in weight (1-way ANOVA), gender, race, cigarette use, and oral birth control use (Chi-square tests) were not significant. Groups differed slightly in age (F (2,42) = 6.56, p < 0.005) with low users being younger than high users (p < 0.005). Since age correlated with some measures of CBF, it was used as a covariate in CBF analyses. Primary analyses were conducted using univariate analyses of variance (ANOVA). The pre- and post-drug salivary caffeine concentrations were analyzed separately with repeated measures 2 (State) x 2 (Drug) x 3 (Caffeine Use) ANOVAs. The same analyses were performed on pre-drug and post-drug measures for respiration rate, end tidal CO2 , O2 saturation, heart rate, and blood pressure. Potential interactions between gender and gray matter CBF were investigated with a 2 (State) x 2 (Drug) x 2 (Sex) ANOVA. There were no significant interactions between gender and any of the main effects or interactions; therefore, the genders were combined in further analyses. The signal to noise ratio of the M0 images were analyzed with a 2 (State) x 2 (Drug) x 3 (Caffeine Use) repeated-measures ANOVA and no significant effects were found. Gray matter CBF was analyzed with a repeated-measures 2 (State) x 2 (Drug) x 3 (Caffeine Use) analysis of covariance (ANCOVA) using age as the covariate. The difference from the mean age was used instead of the raw value, in order to avoid interfering with the main effects (Delaney and Maxwell, 1981). Difference measures in CBF between caffeine states and drug conditions were analyzed with a 2 (State) x 3 (Caffeine Use) and a 2 (Drug) x3 (Caffeine Use) ANCOVA, respectively. Follow-up analyses included two-tailed independent-samples t-tests to measure between-caffeine use group effects, and paired-samples t-tests to measure within-caffeine use group effects. Correlations were performed using two-tailed Pearson's product-moment correlation. |
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| What conflicts of interest were reported? | None were mentioned. |
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| Refid | 19219847 |
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| What were the sources of funding? | This work was supported by NIH grants EB03880, EB004673, DA024950, NS042568, and RR07122. We would like to thank the Center for Biomolecular Imaging, the General Clinical Research Center, and Debra Hege, for their assistance with the collection of data Supported by grants from the National Institutes of Health (EB03880, EB004673, DA024950, NS042568, and RR07122). |
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Results & Comparisons
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