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Study Title and Description

Caffeine reinforces flavour preference in caffeine-dependent, but not long-term withdrawn, caffeine consumers.



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on behavior*?
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Primary Publication Information
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TitleData
Title Caffeine reinforces flavour preference in caffeine-dependent, but not long-term withdrawn, caffeine consumers.
Author EM Tinley,MR Yeomans,PJ Durlach,
Country
Year 2003
Numbers

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Extraction Form: Behavior - Design Details - INCLUDED Studies
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Design Details
Question... Follow Up Answer Follow-up Answer
Refid 12589525
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What outcome is being evaluated in this paper? Behavior
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What is the objective of the study (as reported by the authors)? To examine whether moderate caffeine consumers who have been fully withdrawn from caffeine manifest the flavour conditioning effect.
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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 Staff and students of University of Sussex who had previously completed a general eating and drinking questionnaire for the laboratory and indicated an interest in taking part in experiments were contacted. The questionnaire included sections regarding general drinking and eating habits and a section on daily drink consumption. Caffeine consumption levels were estimated from self-reported daily drink consumption using the following approximations of normal caffeine content: cola=30 mg/can, tea=60 mg/ cup, instant coffee=70 mg/cup and filter coffee=125 mg/cup (adapted from James 1991). Those whose caffeine consumption was between 170 mg/day and 550 mg/day (moderate consumers) were contacted. Exclusion criteria included medical contra-indications (diabetes, taking prescription medication excluding the contraceptive pill), diagnosis of an eating disorder or allergies to any of the ingredients included in the breakfast meal (wheat, nuts, milk, caffeine). The first 52 respondents to fulfill these criteria were recruited, of whom four withdrew before completion of the study. All participants were informed that the purpose of the experiment was an investigation into the effects of long-term withdrawal from caffeine on mood, and written informed consent was obtained prior to participation. The study procedure was approved by the Design The experiment used a mixed design, with participants (between subjects) assigned randomly to one of four groups: 1. Withdrawn for 2 weeks, given placebo in conditioning (WP) 2. Withdrawn for 2 weeks, given caffeine in conditioning (WC) 3. Maintained on caffeine for 2 weeks, given placebo in conditioning (MP) 4. Maintained on caffeine for 2 weeks, given caffeine in conditioning (MC) There were no statistically significant differences in the ages, weights and estimated daily caffeine consumption of the four groups (Table 1). Replacement drinks Throughout the 4-week test period, participants were supplied with drinks that replaced their normal caffeinated tea and coffee consumption. Participants in the maintained groups received caffeinated instant coffee (Dow Egberts Continental brand) and tea (Typhoo brand tea bags), while those in the withdrawn groups received the decaffeinated versions of these products. These products were provided in quantities that matched the self-reported daily usage of these products by each participant, and the administration of caffeinated or decaffeinated versions was double blind. Test drink The drink served during the conditioning phase was Twinings camomile and spiced apple. A pilot study of several potential teas found this to be rated mid-range for pleasantness and highly for novelty. Drinks were made by steeping a tea bag in 200 g boiling water for 2 min and then allowing the drink to cool to 65_x0002_C before serving. Either 70 mg caffeine (Courtin and Warner Ltd) or 70 mg placebo (maltodextrin Cerostar) was added to the fruit tea in a double-blind administration. Caffeine saliva assay A qualitative procedure was used to detect the presence of caffeine in saliva above 8 mM. To obtain the saliva samples, subjects placed a single cotton-wool roll between their molar teeth for 2 min, chewing gently to encourage saliva production. The cotton-wool rolls were then placed in salivettes which were centrifuged at 3500 rpm for 10 min to extract the saliva. Thus it was possible to assess whether subjects had consumed caffeinated drinks, although exact quantities could not be estimated. Procedure All testing was conducted in the Psychopharmacology Unit at Sussex University, and each participant was tested over a 4-week period which was divided into a 2-week caffeine washout period and a further 2 weeks when conditioning trials were conducted. Dietary restrictions for the 4-week period included abstention from all foodstuffs and drinks containing caffeine and any over-the counter medications such as cold and flu remedies known to contain caffeine. Participants were provided with enough tea and coffee replacement drinks to last 1 week at a time, and were told to use these in place of their normal drinks. At the start of the first five sessions participants provided a saliva sample, and salivary caffeine was assayed from samples four and five, at which point the withdrawn group would be predicted to be caffeine free. All data from those participants in the withdrawn group who had measurable salivary caffeine in the samples from week two were discarded since they must have violated the caffeine restrictions. In order to assess effects of the caffeine intake restrictions on mood, participants completed an 18-item mood questionnaire immediately after providing the saliva sample. The moods assessed included those previously shown to be sensitive to caffeine manipulations (Richardson et al. 1995): jittery, energetic, tired, lively, and clear-headed as well as ratings for headache, hunger and thirst. These were embedded among other mood adjectives (happy, friendly, tense, drowsy, cheerful, calm, uncertain, dejected, placid, confident, angry, and muddled), and ratings were made on a 100-mm visual analogue scale, anchored at 0 mm= ‘not at all’ and 100 mm= ‘extremely’. On the first test session, participants were asked to select their preferred beverage (tea or coffee) to be consumed at breakfast, and this drink was provided (in decaffeinated form in the withdrawn group and caffeinated form in the maintained group) on all five sessions. Data analysis Three subjects were excluded from the analysis, one from group MC who admitted during debriefing drinking coffee other than that provided, and a further two subjects (one from group WC, one from group WP) whose caffeine assay results from week 2 were positive, confirming they had not complied with the caffeine restrictions. Thus, analysis was conducted on 10 subjects in group MC, 13 subjects in the group MP, 10 subjects in group WC and 11 subjects in the group WP. Initial withdrawal period test days 1–5 To evaluate whether liking and novelty ratings for the caffeinated and decaffeinated versions of the drink consumed at breakfast differed between maintained and withdrawn groups, or changed during the initial withdrawal period, a two-way, repeated-measures ANOVA was conducted with group (withdrawn vs maintained) and session (1–5) as factors. Overall change in liking for the breakfast drink during this period was measured by subtracting the pleasantness score on session 5 from that on session 1. The effect of acute and chronic caffeine withdrawal were examined by comparing baseline differences between the maintained and withdrawn groups. No food and drink restrictions were placed on subjects prior to the first session; thus, differences were assessed on sessions 2–5 using a two-way, repeated-measures ANOVA, with group (withdrawn vs maintained) and session (_x0003_4) on each of the moods previously found to reflect caffeine withdrawal symptoms (jittery, energetic, tired, lively, clear-headed and headache). To assess the effect of ingestion of the caffeinated and non-caffeinated tea/coffee, repeated- measures ANOVAs were conducted on each mood with condition (between subject), session (_x0003_4) and time (before and after) as within-subject factors. Since mood changes were not the primary focus of this study, we only reported significant changes relevant to the interpretation of the drink pleasantness data. Mood changes during the conditioning phase of the study were not directly relevant to the hypotheses under test. However, ratings previously shown to be sensitive to caffeine (jittery, energetic, tired, lively, clear-headed and headache) were analysed to test whether the inclusion of caffeine in the fruit tea drink resulted in caffeine-specific changes in mood. Since one group were now fully withdrawn from caffeine and one group were maintained, absolute ratings were used since withdrawal state could have affected baseline mood evaluations. These were contrasted across the four conditioning days with group and drug as between-subject factors using three-way ANOVA, and hunger and thirst were also assessed to test for spurious differences that could have indirectly influenced drink evaluations.
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How many outcome-specific endpoints are evaluated? 6
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) jittery
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List additional health endpoints (separately). drowsy
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List additional health endpoints (separately) dejected
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Notes Additional adverse endpoints were: angry and muddled.
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Clinical Clinical
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Physiological
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Other
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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? Subjective
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Optional: Name of Method or short description mood questionnaire, visual analogue scale (VAS)
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Caffeine (general) Caffeine (general)
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Coffee
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Chocolate
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Energy drinks
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Gum
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Medicine/Supplement
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Soda
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Tea Tea
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Measured Measured
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Self-report
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Children
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Adolescents
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Adults Adults
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Pregnant Women
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) placebo controlled (tea alone, no caffeine added) vs 70 mg caffeine added to tea
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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) N/A
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Provide a general description of results (as reported by the authors). With regard to baseline differences, only headache ratings showed an effect of group (F1,42=4.27, P<0.05), with the maintained group recording higher levels of headache than the withdrawn group (Fig. 1). In addition, headache and clear-headed ratings were affected by caffeine ingestion. A time_x0003_ condition interaction for headache (F1,42=4.02, P=0.051) revealed that before ingestion of the tea/coffee, the maintained group had significantly higher headache ratings than the withdrawn group (t43=2.922, P<0.01), yet there was no difference between groups after the drink had been consumed. The only rated mood significantly affected by ingestion of caffeine was energetic (Table 3).
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Did the authors perform a dose-response analysis (or trend/related analysis)? No
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What were the authors's observations re: trend analysis?
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What were the author's conclusions? Analysis of the mood data in the current experiment did not indicate that the withdrawn group experienced any adverse effects of acute caffeine consumption. In fact, only positive mood changes were seen in response to the caffeinated fruit tea with increased energy and a tendency towards increased liveliness and a reduction in headaches, irrespective of whether the recipient was acutely or chronically withdrawn.
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What were the sources of funding? This work was supported by a BBSRC studentship to Elizabeth Tinley with additional funding from Unilever plc.
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What conflicts of interest were reported? None reported
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Does the exposure (dose) need to be standardized to the SR? No
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Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).
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List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot.  Characterize value as LOAEL/NOAEL, etc. if possible.  headache - NOAEL = 70 mg jittery - NOAEL = 70 mg tired - NOAEL = 70 mg tense - NOAEL = 70 mg angry - NOAEL = 70 mg dejected - NOAEL = 70 mg drowsy - NOAEL = 70 mg muddled - NOAEL = 70 mg
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Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot. single dose No effects seen at levels lower than Nawrot. The group that was maintained on caffeine had higher levels of headache that were reduced by consuming caffeine. No other adverse moods were affected by caffeine ingestion.
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What is the importance of the study with respect to the adverseness of the outcome? Important
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